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, Jacqueline Stephanie Kameni Njapdounke, Jean Jules Fifen, , Lucie Josiane Ojong, Antoine Kavaye Kandeda, Elisabeth Ngo Bum
Published: 1 February 2018
Journal of ethnopharmacology, Volume 212, pp 18-28; https://doi.org/10.1016/j.jep.2017.09.042

Abstract:
Senna spectabilis (Fabaceae) is one of the medicinal plants used in Cameroon by traditional healers to treat epilepsy, constipation, insomnia, anxiety. The present study aimed to investigate the anticonvulsant effects of Senna spectabilis decoction induced by maximal electroshock (MES), pentylenetetrazole (PTZ), pilocarpine (PC) and its possible action mechanisms in animal models using flumazenil (FLU), methyl-ß-carboline-3-carboxylate (BC) and bicuculline (BIC). Senna spectabilis decoction (106.5 and 213.0mg/kg) antagonized completely tonic-clonic hind limbs of mice induced by MES. The lowest plant dose (42.6mg/kg) provided 100% of protection against seizures induced by PTZ (70mg/kg). Administration of different doses of the plant decoction antagonized seizures induced by PC up to 75%, causing a dose dependent protection and reduced significantly the mortality rate induced by this convulsant. Both FLU and BC antagonize strongly the anticonvulsant effects of this plant and are unable to reverse totally diazepam or the plant decoction effects on inhibiting seizures. The animals did not present any sign of acute toxicity even at higher doses of the plant decoction. In conclusion, Senna spectabilis possesses an anticonvulsant activity. We showed that its decoction protects significantly mice against seizures induced by chemicals and MES, delays the onset time and reduces mortality rate in seizures-induced. Moreover, the plant decoction could interact with GABAA complex receptor probably on the GABA and benzodiazepines sites.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 217-223; https://doi.org/10.1016/j.jep.2017.09.041

Abstract:
Perillae Herba is a perennial plant that is widely distributed throughout Asia. The leaves of Perillae Herba have been widely used to treat various diseases, such as cold due to wind-cold, headache, cough, abdominal fullness, distention, and fish and crab poisoning.To assess the anti-inflammatory activity of Perillae Herba leaf ethanolic extract (PHE) in human keratinocytes, we measured the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-induced mRNA expression and production of proinflammatory chemokines such as thymus and activation-regulated chemokines; regulated on activation, normal T cell expressed and secreted; interleukin (IL)-6; and IL-8 in HaCaT cells. We evaluated the ability of PHE to decrease the expression of proinflammatory marker proteins, such as mitogen-activated protein kinase (MAPK), STAT-1, and NK-κB, using western blot analysis and immunocytochemistry.PHE inhibited activation of p38, ERK, and JNK and suppressed the phosphorylation of STAT-1 and NK-κB in TNF-α/IFN-γ-stimulated HaCaT cells. PHE also suppressed chemokine mRNA and protein levels in TNF-α/IFN-γ-stimulated HaCaT cells. PHE appears to regulate chemokine formation by inhibiting activation of MAPK, as well as the STAT-1 and NK-κB pathways.PHE suppresses the expression and production of TNF-α/IFN-γ-stimulated proinflammatory chemokines by blocking NF-κB, STAT-1, and MAPK activation.
Published: 1 June 2018
Journal of ethnopharmacology, Volume 220, pp 188-196; https://doi.org/10.1016/j.jep.2017.09.036

Abstract:
PA may act as a Ca antagonist to exert an intensively vasorelaxant effects through endothelium-independent pathway, and its mechanisms underlying the vasoactivities seem to be associated with the blockade of extracellular Ca influx through VDCCs and ROCCs in vascular smooth muscle cells (VSMCs) membrane and intracellular Ca releases through IPR- and RYR-mediated Ca channels in sarcolemma.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 267-277; https://doi.org/10.1016/j.jep.2017.09.038

Abstract:
Current HIV therapies do not act on latent cellular HIV reservoirs; hence they are not curative. While experimental latency reversal agents (LRAs) can promote HIV expression in these cells, thereby exposing them to immune recognition, existing LRAs exhibit limited clinical efficacy and high toxicity. We previously described a traditional 3-step medicinal plant regimen used for HIV/AIDS management in Northern Botswana that inhibits HIV replication in vitro. Here we describe use of one component of the regimen that additionally contains novel phorbol esters possessing HIV latency-reversal properties.We sought to document experiences of traditional medicine users, assess the ability of traditional medicine components to reverse HIV latency in vitro, and identify pure compounds that conferred these activities.Experiences of two HIV-positive traditional medicine users (patients) were documented using qualitative interview techniques. Latency reversal activity was assessed using a cell-based model (J-Lat, clone 9.2). Crude plant extracts were fractionated by open column chromatography and reverse-phase HPLC. Compound structures were elucidated using NMR spectroscopy and mass spectrometry.Patients using the 3-step regimen reported improved health over several years despite no reported use of standard HIV therapies. Crude extracts from Croton megalobotrys Müll Arg. ("Mukungulu"), the third component of the 3-step regimen, induced HIV expression in J-lat cells to levels comparable to the known LRA prostratin. Co-incubation with known LRAs and pharmacological inhibitors indicated that the active agent(s) in C. megalobotrys were likely to be protein kinase C (PKC) activator(s). Consistent with these results, two novel phorbol esters (Namushen 1 and 2) were isolated as abundant components of C. megalobotrys and were sufficient to confer HIV latency reversal in vitro.We have identified novel LRAs of the phorbol ester class from a medicinal plant used in HIV/AIDS management. These data, combined with self-reported health effects and previously-described in vitro anti-HIV activities of this traditional 3-step regimen, support the utility of longitudinal observational studies of patients undergoing this regimen to quantify its effects on plasma viral loads and HIV reservoir size in vivo.
, Isaac K. Amponsah, , , Paul A. Steenkamp, Ntakadzeni E. Madala,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 207-216; https://doi.org/10.1016/j.jep.2017.09.030

Abstract:
Leishmaniasis is one of the neglected tropical disease caused by a protozoan of the genus Leishmania transmitted by sandflies. High cost and lack of oral formulation of existing drugs, rapid developments of resistance by the parasite coupled with serious side effects require new treatments to augment or replace currently available therapies. The major merits of herbal medicine seem to demonstrate perceived efficacy, low incidence of serious adverse effects and low cost. Erythrophleum plants possess beneficial biological properties and, as such, characterization of the bioactive components of these plants is imperative. Previous work has shown an overwhelming presence of cassaine alkaloids in these plants. However, amongst these plants, the African based specie (Erythrophleum ivorense) is the least studied.In the current study, the in vitro anti-leishmanial activity of the crude extract, its fractions and isolated compounds were evaluated using direct counting assay of promastigotes of Leishmania donovani using amphotericin B as positive control.The anti-leishmanial activity of E. ivorense extract was evaluated in vitro against the promastigote forms of Leishmania Donovani using a direct counting assay based on growth inhibition. Different crude extracts from ethyl acetate, pet-ether, and methanol as well as pure isolated compounds of E. ivorense: Erythroivorensin, Eriodictyol and Betulinic acid were screened. To know the possible components of the active methanolic extract, attempt was made to elucidate the extract using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS).This afforded a weak pet-ether fraction, a moderately active ethyl acetate fraction and a significantly active methanol fraction (IC50 = 2.97μg/mL) compared to Amphotericin B (IC50 = 2.40±0.67μg/mL). The novel diterpene erythroivorensin, betulinic acid and the flavanone Eriodictyol, from the ethyl acetate fraction, showed weak activity. UPLC-QTOF-MS/MS was used to identify the cassaine diterpenoids from the active methanol fraction. Here, 10 compounds of this type were putatively identified from the ethanol crude extract.The fragmentation mechanism of these metabolites is also proposed and are expected to serve as reference template for identification of these and related compounds in future. The presence of these compounds is an indication that they are an inherited and evolutionary component of plants belonging to the Erythrophleum genus. Our results further present another dimension where these compounds and their relative abundances can be used as chemo-taxonomical bio-markers of the genus. The present study also successfully demonstrated/re-affirmed the use of UPLC-QTOF-MS/MS as a robust technique for the characterization of natural products.
Lorena Noemi Alamilla-Fonseca, , Jaime Zamora-Chimal, Rocely Buenaventura Cervantes-Sarabia, Adelina Jiménez-Arellanes, ,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 180-187; https://doi.org/10.1016/j.jep.2017.09.037

Abstract:
We conclude that Cleoserrata serrata extract is potentially an optimal treatment alternative for patients with cutaneous leishmaniasis infected with Leishmania mexicana, since it controls both the parasite as well as bacterial co-infections. Furthermore, it can be applied topically. The precise metabolites responsible for the anti-Leishmania and anti-bacterial effects remain to be established.
Qing Tang, Sheng Yang, Jie Tong, Xu Li, Junjie Wu, Senhong Wang, Jifen Zhang, Yi Chen,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 278-284; https://doi.org/10.1016/j.jep.2017.09.035

Abstract:
The ZG extract was quality controllable by assaying for asperosaponin Ⅵ, TSG, total tannins, total saponins and total flavonoids. It could promote the hemostasis of mice in vivo, as well as the uterine contractions of rats in vitro. Therefore, it may be a promising preparation for clinical treatment of perimenopausal dysfunctional uterine bleeding.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 285-294; https://doi.org/10.1016/j.jep.2017.09.031

Abstract:
Uncaria tomentosa (Willd.) DC. (Rubiacee), also known as uña de gato, is a plant that grows wild in the upper Amazon region of Peru and has been widely used in folk medicine to treat several health conditions including cancer. We have produced an aqueous extract from Uncaria tomentosa (UT-ex) and analyzed its effects on squamous carcinoma cells and immortalized HaCaT keratinocytes. Squamous cell carcinoma (SCC) is an uncontrolled growth of abnormal cells arising in the skin's squamous layer of epidermis. When detected at an early stage, SCCs are almost curable, however, if left untreated, they can penetrate the underlying tissue and become disfiguring. We have evaluated cell proliferation, apoptosis and the level of reactive oxygen species following UT-ex treatment. UT-ex affected cell cycle progression and reduced cell viability in a dose and time-dependent manner. From a mechanistic point of view, this delay in cell growth coincided with the increase of reactive oxygen species (ROS). Furthermore, PARP1 cleavage was associated to the reduction of Y-box binding protein 1 (YB-1) 36kDa, a nuclear prosurvival factor involved in DNA damage repair. These data indicate that UT-ex-induced cell death can be ascribed, at least in part, to its ability both to induce oxidative DNA damage and antagonize the mechanism of DNA repair relying upon YB-1 activity. They also show that non metastatic SCCs are more susceptible to UT-ex treatment than untransformed keratinocytes supporting the use of UT-ex for the treatment of precancerous and early forms of squamous cell carcinomas. Preliminary chemical investigation of UT-ex revealed the presence of hydrophilic low-medium molecular weight metabolites with anticancer potential towards squamous carcinoma cells.
Chunyu Wu, , Pei Liu, Yuqing Ge,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 89-100; https://doi.org/10.1016/j.jep.2017.09.033

Abstract:
Triple-negative breast cancer (TNBC) often presents with a high histological grade and high malignancy, which greatly contribute to patient morbidity and mortality. Rhizoma Amorphophalli exhibits many biological and pharmacological activities, but its potential as a therapeutic agent for the treatment of metastatic TNBC patients remains poorly understood.The aim of this study was to determine whether Rhizoma Amorphophalli inhibits metastasis in the human TNBC MDA-MB-231 cell line.CCK-8 and colony formation assays were adopted for the analysis of cell activity and cell proliferation, respectively. Flow cytometry was used for cell cycle analysis. Wound healing and transwell assays were performed to assess cell migration and invasion, respectively. PI3K/Akt/mTOR signaling pathways were analyzed through western blotting. Breast cancer cell metastasis to the lung in a xenograft model was evaluated by in vivo fluorescence imaging. A GC-MS analysis was performed to determine the main components of the petroleum ether fraction from the ethanol extract of Rhizoma Amorphophalli (abbreviated RhA).RhA significantly reduced breast cancer cell viability and proliferation. The flow cytometry analysis indicated that RhA induced MDA-MB-231 cell arrest at the S phase. Additionally, RhA decreased MDA-MB-231 cell migration and invasion and inhibited the PI3K/Akt/mTOR signaling pathway. In addition, mice treated with RhA exhibited a significant reduction in tumor infiltration and a decrease in breast cancer cell metastasis to the lung. The GC-MS analysis results showed that RhA contained a large number of unsaturated fatty acids, such as octadecadienoic acid (linoleic acid), octadecatrienoic acid (linolenic acid), and oleate, which might represent the anticancer components of the extract.The results of this study suggest that RhA has potential as a therapeutic candidate for metastatic TNBC treatment.
Neha Sharma, Ashok Kumar, P.R. Sharma, Arem Qayum, , Prabhu Dutt, , Vivek Gupta, , , et al.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 295-310; https://doi.org/10.1016/j.jep.2017.09.034

Abstract:
Tinospora cordifolia is a miraculous ayurvedic herb used in the treatment of innumerable diseases such as diabetes, gonorrhoea, secondary syphilis, anaemia, rheumatoid arthritis, dermatological diseases, cancer, gout, jaundice, asthma, leprosy, in the treatment of bone fractures, liver & intestinal disorders, purifies the blood, gives new life to the whole body; (rejuvenating herb) and many more. Recent studies have revealed the anticancer potential of this plant but not much work has been done on the anticancer chemical constituents actually responsible for its amazing anticancer effects. This prompted us to investigate this plant further for new potent anticancer molecules.The present study was designed to isolate and identify new promising anticancer candidates from the aqueous alcoholic extract of T. cordifolia using bioassay-guided fractionation.The structures of the isolated compounds were determined on the basis of spectroscopic data interpretation and that of new potent anticancer molecule, TC-2 was confirmed by a single-crystal X-ray crystallographic analysis of its corresponding acetate. The in vitro anti-cancer activity of TC-2 was evaluated by SRB assay and the autophagic activity was investigated by immunofluorescence microscopy. Annexin-V FITC and PI dual staining was applied for the detection of apoptosis. The studies on Mitochondrial Membrane potential and ROS (Reactive oxygen species) production were also done.Bioassay guided fractionation and purification of the aqueous alcoholic stem extract of Tinospora cordifolia led to the isolation of a new clerodane furano diterpene glycoside (TC-2) along with five known compounds i.e. cordifolioside A (β-D-Glucopyranoside,4-(3-hydroxy-1-propenyl)- 2,6-dimethoxyphenyl 3-O-D-apio-β-D-furanosyl) (TC-1), β-Sitosterol(TC-3), 2β,3β:15,16-Diepoxy- 4α, 6β-dihydroxy-13(16),14-clerodadiene-17,12:18,1-diolide (TC-4), ecdysterone(TC-5) and tinosporoside(TC-6).TC-2 emerged as a potential candidate for the treatment of colon cancer.The overall study on the bioassay guided isolation of T.cordifolia identified and isolated a new clerodane furano diterpenoid that exhibited anticancer activity via induction of mitochondria mediated apoptosis and autophagy in HCT116 cells. We have reported a promising future candidate for treating colon cancer.
Peng Ji, , Yongli Hua, Xiaosong Zhang, Wanling Yao, Qi Ma, , Yanqiao Wen, Chaoxue Yang
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 101-116; https://doi.org/10.1016/j.jep.2017.09.028

Abstract:
Angelica sinensis (AS), root of Angelica sinensis (Oliv.) Diels, an important kind of Chinese traditional herbal medicine, has been used for women to enrich the blood for thousands of years. It is mainly distributed in Gansu province of China. According to Traditional Chinese medicine usage, unprocessed AS (UAS) and its 4 kinds of processed products (ASs) are all used to treat different diseases or syndromes. The difference among the enriching-blood effects of ASs is unclear. And their exact mechanisms of enriching the blood are not fully understood.In this study, our aim is to compare the enriching-blood effect and explain the related mechanism of ASs, to lay the foundation for the blood deficiency diagnosis and the rational use of ASs in the clinic.ASs were used to intervene the blood deficiency syndrome model mice induced by acetyl phenylhydrazine (APH) and cyclophosphamide (CTX). A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of ASs was established. The blood routine examination, ATPase, glucose-6-phosphate dehydrogenase, methemoglobin, glutathion peroxidase, glutathione reductase, and erythropoietin were measured. Two biofluids (plasma and urine) obtained from mice were analyzed with GC-MS. Distinct changes in metabolite patterns of the two biofluids after mice were induced by APH and CTX, and mice were intervened with ASs were analyzed using partial least squares-discriminant analysis. Potential biomarkers were found using a novel method including variable importance in the projection (VIP) >1.0, volcano plot analysis, and significance analysis of microarray.The results of hematological, biochemical parameters and the integrated metabolomics all showed the blood deficiency syndrome model was built successfully, ASs exhibited different degree of enriching-blood effect, and AS pached with alcohol (AAS) exhibited the best enriching-blood effect. 16 metabolites in the plasma and 8 metabolites in the urine were considered as the potential biomarkers. These metabolites were involved in 7 metabolic pathways which were concerned with the different enriching-blood effect mechanisms of ASs. The correlation analysis results confirmed L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine) and Cholesterol (urine) were strong positive or negative associated with biochemical indicators.The enriching-blood effects of ASs are different. The pathological mechanisms of blood deficiency syndrome and the enriching-blood effect mechanism of ASs are involved in 7 metabolic pathways. L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine), Cholesterol (urine) are four important biomarkers being related to the enriching-blood effect of ASs. The combination of VIP, volcano plot analysis and significance analysis of microarray is suitable for screening biomarkers in metabolomics study. They can lay the foundation for clinical practice.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 117-125; https://doi.org/10.1016/j.jep.2017.09.017

Abstract:
Myrianthus arboreus P. Beauv. is a tropical tree used in African folk medicine, including for diabetes. However, little research has yet been conducted to support this ethnopharmacological use of this plant. The present study sought to determine the antidiabetic potential of root bark extracts through cell-based bioassays of liver and muscle glucose homeostasis.Four extracts were obtained from crude root bark powder: 1 aqueous (AQ), 2 ethanol (EtOH), 3 alkaloid enriched (Alk) (obtained from methanol extract) and 4 dichloromethane (Dic) extracts. Moreover, extract 2 was further separated into two fractions: 2.1 ethyl acetate (EAc) and 2.2 hexane (Hex). To assess the antidiabetic activity of the plant extracts, inhibition of glucose-6-phosphatase (G6Pase), stimulation of glycogen synthase (GS) and modulation of glucose uptake were determined in cultured H4IIE and HepG2 hepatocytes as well as C2C12 myocytes, respectively. Phosphorylation of three kinases, AMP-activated protein kinase (AMPK), Akt and Glycogen Synthase Kinase-3 (GSK-3) were probed by Western blot.M. arboreus extracts/fractions did not stimulate glucose uptake in C2C12 cells albeit 2.2 (Hex) fraction showed a mild positive tendency. In contrast, extract 2 and its fractions as well as extract 3 were able to decrease hepatocyte G6Pase activity. Their effect on G6Pase activity involved both Akt and AMPK phosphorylation. No significant correlation was observed between activation of Akt and inhibition of G6Pase (R(2) = 0.50 p < 0.14), whereas that between stimulation of AMPK and inhibition of G6Pase was statistically significant (R(2) = 0.75 p < 0.05). On the other hand, extract 2, its fraction 2.2 and extract 3 were able to stimulate GS through GSK-3 phosphorylation. A high correlation was observed between the ability of M. arboreus extracts and fractions to phosphorylate GSK-3 and modulate GS activity (R(2)=0.81 p < 0.01). Extract 2 and its fraction 2.2 together with extract 3 were the only plant products to simultaneously and potently regulate G6Pase and GS, the key players of hepatic glucose homeostasis.Overall, these data support the traditional antidiabetic uses of the root bark of M. arboreus.
Published: 21 September 2017
Journal of ethnopharmacology, Volume 211, pp 171-179; https://doi.org/10.1016/j.jep.2017.09.026

Abstract:
Ethnopharmacological relevance As documented in a Vietnamese traditional medical encyclopedia, Syzygium formosum (Wall.) Masam leaves have been routinely used among indigenous Vietnamese people for treatment of various allergy-like symptoms including dermatitis and rhinitis. Aim of the study: Anti-allergic activity of S. formosum leaves was examined with a mouse model of chicken ovalbumin (cOVA)-induced food allergy, and mechanisms underlying the anti-allergic effect were explored. Material and methods BALB/c mice were administered i.p. cOVA (20<!-- --> <!-- -->μg) plus alum (2<!-- --> <!-- -->mg) twice on day 0 and 14 for sensitization (immunization). Two weeks after the second immunization, the mice were administered cOVA (50<!-- --> <!-- -->mg) p.o. 5 times every 3 days to induce food allergy symptoms (i.e., anaphylaxis, diarrhea, and drop in the body temperature). Ethanol extract of dried leaves of S. formosum (80<!-- --> <!-- -->mg/kg or 200<!-- --> <!-- -->mg/kg body weight) was administered p.o. daily during the induction (challenge) period. Results: Treatment with the S. formosum leaves ethanol extract ameliorated the allergic symptoms to a significant extent and in a dose-dependent manner. The treatment also resulted in a significant improvement in the inflammatory lesion in the small intestine and reduction in the numbers of mast cells and eosinophils recruited to the lesion. The treatment also brought about a significant reduction in the levels of Th2 cytokines produced by the mesenteric lymph node cells cultured ex vivo with cOVA. The passive anaphylaxis experiment also showed that the extract treatment impaired the mast cell function. Conclusion: Our study provides a scientific basis for the traditional (indigenous) use of the S. formosum leaves extract for the treatment of various allergy symptoms in Vietnam. In addition, the results show that the extract has activities to suppress antigen-specific Th2 T cell immune responses and the mast cell function, which are directly related with its anti-allergic effect.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 70-77; https://doi.org/10.1016/j.jep.2017.09.027

Abstract:
Copaifera malmei Harms (Fabaceae), known mainly as óleo-mirim, is a native and endemic plant found in the states of Mato Grosso and Goiás of Brazil. The plant's leaves infusion is popularly used by riverine communities of the northern Araguaia microregion, Mato Grosso, Brazil, for the treatment of gastric ulcers and inflammatory diseases of the respiratory tract. The gastric antiulcer activity of the standardized leaves infusion extract of Copaifera malmei (SIECm) in rodents has been reported. The objective of this study was to advance the investigatation of the safety profile of SIECm by evaluating the genotoxicity and subchronic toxicity using in vitro and in vivo experimental models.SIECm was prepared by infusion, by incubating the powdered dried leaves material in boiled water for 15min. In vitro genotoxicity of SIECm (10, 30 or 100μg/mL) was assessed by micronucleus and comet tests using Chinese hamster ovary (CHO-k1) epithelial cells. The evaluation of subchronic toxicity profile was performed by daily oral administration of SIECm (100, 400 or 1000mg/kg) to Wistar rats for 30 days. Clinical observations of toxicological related parameters were done every 6 days. After the treatment period, blood was collected for hematological and biochemical analyzes, and some organs were removed for macroscopic and histopathological analysis.In the micronucleus assay, SIECm demonstrated anti-mutagenic activity. In the comet assay, SIECm presented anti-genotoxic effect preventing DNA damage at all the three concentrations tested with pre-treatment, while the same effect was only observed in the co-treatment at the lowest concentration. Post-treatment with SIECm increased the genetic damage induced by hydrogen peroxide (H2O2) at the highest concentration. In the subchronic toxicity test, few changes were observed, such as increase in feed consumption in the group of animals treated with 100mg/kg of the SIECm, which reversed after 6 days. There were no macroscopic, histological and relative weights changes in the organs of animals treated with SIECm. No toxicologically relevant changes were observed in the hematological analysis. Subchronic administration of SIECm reduced levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in animals treated with 100mg/kg and serum triglyceride levels at 400 and 1000mg/kg. However, the hematological and biochemical changes observed are within the physiological ranges for this animal species.The results demonstrate that SIECm is not genotoxic, and does not present toxicity when used orally for up to 30 days. In addition, it showed protection to the genetic damage induced by H2O2. The SIECm therefore has a high safety margin for therapeutic use.
Published: 1 February 2018
Journal of ethnopharmacology, Volume 212, pp 36-42; https://doi.org/10.1016/j.jep.2017.09.015

Abstract:
Ophidian accidents are a serious public health problem in Argentina; the Bothrops species is responsible for 97% of these accidents, and in particular, B. diporus is responsible for 80% of them. In the northeast of the country (Corrientes Provinces), Cissampelos pareira L. (Menispermaceae) is commonly used against the venom of B. diporus; its use is described in almost all ethnobotanical literature from countries where the plant grows,.In this study, the in vitro and in vivo antivenom activities of C. pareira extracts were evaluated against B. diporus venom, with a particular focus on the local effects associated with envenoming. The seasonal influence on the chemical composition of the active extracts was also studied, in order determine the associated range of variability and its influence on the antivenom activity.This research was conducted using aerial parts (leaves, flowers, tender stems) and roots of Cissampelos pareira collected from two different phytogeographic regions of Corrientes (Argentina); Paso de la Patria and Lomas de Vallejos. In addition, to perform a seasonal analysis and to evaluate the metabolic stability, material was collected at three different growth stages. In vivo and in vitro anti-snake venom activities were tested, and a bio-guided chromatographic separation was performed in order to determine the active chemicals involved. The fractions obtained were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and the chemical profile of the most active constituent was analyzed by ultra high-performance liquid chromatography coupled to quadrupole/high-resolution mass spectrometry (Q-Orbitrap). (UHPLC-MS).The alcoholic extract was found to be the most active The bio-guided fractionation allowed selection one fraction to be analyzed by UHPLC-MS in order to identify the components responsible for the activities found; this identified five possible flavonoids.Our studies of the activity of C. pareira against the venom of B. diporus have confirmed that this species possesses inhibitory effects in both in vitro and in vivo models. Moreover, the present data demonstrate that certain flavonoids may mitigate some of the venom-induced local tissue damage.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 17-28; https://doi.org/10.1016/j.jep.2017.09.024

Abstract:
The traditional uses of Corydalis dubia, Ajania nubigena and Pleurospermum amabile in the Bhutanese traditional medicine for treating disorders related to inflammatory conditions and the in vitro anti-inflammatory activity of their crude extracts inspired the isolation and the investigation of anticolitic properties of four pure compounds.Three medicinal plants were collected from Himalayan Mountains of Bhutan. Capnoidine and scoulerine were isolated from C. dubia, linalool oxide acetate from A. nubigena and isomyristicin from P. amabile using natural product isolation protocols. Four compounds were investigated for their anti-inflammatory activities against IBD-colitis using chemically induced (TNBS) mice model of colitis. Capnoidine conferred the best preliminary protection against TNBS-induced colitis in mice and we have conducted in-depth pharmacological investigation of this compound including clinical symptoms, pathological signs, cytokine profiles, histological structure and inflammasomes using relevant bioassay protocols.Capnoidine-treated mice had significantly: a) improved clinical symptoms (body weight loss, mobility, piloerection and faecal consistency); b) reduced colon pathology (adhesion, edema, ulceration, and colon length); c) altered inflammatory cytokines profiles within the colons; d) reduced levels of p-IκB-α (Ser32) and p-NF-κB p65 (Ser536) and e) reduced histological inflammation in the colon when compared with mice administered TNBS only.Capnoidine presents as a potential new anti-inflammatory drug lead candidate for diseases where current standard-of-care often fails and is associated with major side effects. It also validates the traditional uses of C. dubia against inflammatory conditions and underlines the value of pursuing bioactive compounds derived from traditionally used ethnobotanical medicines.
, Shakir Saleem, Tanveer Ahmad, , Fahad A. Al-Abbasi, Vikas Kumar,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 394-399; https://doi.org/10.1016/j.jep.2017.09.012

Abstract:
Lantana camara is a popular invasive weed utilized in the management of ulcer in different part of world. Study of specific compound present in this plant responsible for their antulcer activity is main topic of concern. Current study designed for evaluation of the antiulcer activity of oleane-12-en-3β-ol-28-oic acid 3β-D-glucopyranoside (OAG) from Lantana camara L.Antiulcer activity was carried out on NSAID's (Aspirin) and ethanol induced ulcer model. The efficacy of the OAG on ulcer index, percentage protection and gastric acid secretion were evaluated.Ulcer protection percentage (38.37%) was significant (P < 0.001) higher in the groups treated with the higher OAG dose (50 mg/kg), it also recover the mucosa with no redness, no inflammation, mild dilation of blood vessels. OAG significantly (P<0.01 and P<0.001) reduce acidity, free acidity and gastric acid volume. It also significantly (P<0.01) increases the pH of stomach.On the basis of results, it can be concluded that OAG shows significant gastroprotective activity by gastric acid secretion inhibition and afford protection against gastric mucosal damage. Further increase of prostaglandin E2 level establishes the mechanism of antiulcer activity of OAG.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 311-328; https://doi.org/10.1016/j.jep.2017.09.018

Abstract:
The geographical and ecological specificity of the Balkan Peninsula has resulted in the development of a distinct diversity of medicinal plants. In the traditional culture of the Balkan peoples, plants have medicinal, economic and anthropological/cultural importance, which is reflected in the sound knowledge of their diversity and use. This study analyses the traditional use of medicinal plants in the treatment of wounds and the pharmacological characteristics of the most frequently used species.A detailed analysis of the literature related to ethnobhe uses of medicinal plants in the Balkan region was carried out. Twenty-five studies were analysed and those plants used for the treatment of wounds were singled out.An ethnobotanical analysis showed that 128 plant species (105 wild, 22 cultivated and 1 wild/cultivated) are used in the treatment of wounds. Their application is external, in the form of infusions, decoctions, tinctures, syrups, oils, ointments, and balms, or direct to the skin. Among those plants recorded, the most commonly used are Plantago major, Hypericum perforatum, Plantago lanceolata, Achillea millefolium, Calendula officinalis, Sambucus nigra, Tussilago farfara and Prunus domestica. The study showed that the traditional use of plants in wound healing is confirmed by in vitro and/or in vivo studies for P. major and P. lanceolata (3 laboratory studies for P. major and 2 for P. lanceolata), H. perforatum (5 laboratory studies and 3 clinical trials), A. millefolium (3 laboratory studies and one clinical trial), C. officinalis (6 laboratory studies and 1 clinical trial), S. nigra (3 laboratory studies) and T. farfara (one laboratory study).The beneficial effects of using medicinal plants from the Balkan region to heal wounds according to traditional practices have been proven in many scientific studies. However, information on the quantitative benefits to human health of using herbal medicines to heal wounds is still scarce or fragmented, hindering a proper evaluation. Therefore, further studies should be aimed at isolating and identifying specific active substances from plant extracts, which could also reveal compounds with more valuable therapeutic properties. Furthermore, additional reliable clinical trials are needed to confirm those experiences encountered when using traditional medicines. A combination of traditional and modern knowledge could result in new wound-healing drugs with a significant reduction in unwanted side effects.
Cleide Adriane Signor Tirloni, , Thainá De Almeida Tomazetto, , , Ariany Carvalho dos Santos, , Jane Manfron Budel, ,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 47-57; https://doi.org/10.1016/j.jep.2017.09.020

Abstract:
Although Luehea divaricata Mart. (Malvaceae) is popularly used by the population of the Brazilian Pantanal for the treatment of different types of kidney diseases, no study has been carried out to prove this ethnobotanical indication.To investigate the possible cardiorenal effects of an herbal preparation obtained from L. divaricata leaves.First, to provide quality control standards, a detailed morphological and microchemical characterization of L. divaricata leaves was performed. Then, the purified aqueous extract was obtained from the leaves of this species (ESLD) and a thorough phytochemical characterization was performed. Subsequently, acute oral toxicity test was performed after single administration of different doses (5, 50, 300, 2000 mg/kg) in male and female Wistar rats. Finally, the diuretic, hypotensive and antioxidant properties of ESLD (30, 100, 300mg/kg) were evaluated after acute and prolonged treatment and the role of angiotensin converting enzyme, aldosterone, vasopressin, and nitric oxide in these effects was investigated.Analyses performed by liquid chromatography-mass spectrometry showed that the main secondary metabolites present in ESLD were flavonol O-glycosides and flavone C-glycosides. Acute and prolonged treatment with ESLD was able to expressively increase urinary volume and electrolyte excretion. Mean blood pressure and systolic blood pressure were also significantly reduced after acute treatment. Moreover, treatment with ESLD was able to reduce thiobarbituric acid reactive species and increase serum nitrate levels.The data obtained showed that ESLD has an important diuretic and hypotensive effect, which is probably dependent on the reduction of oxidative stress and increased bioavailability of nitric oxide.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 9-16; https://doi.org/10.1016/j.jep.2017.09.019

Abstract:
The preparations of teas and syrups using Duguetia furfuracea have been used in folk medicine to treat rheumatism and back pain. Several rheumatic diseases are anti-inflammatory and are treated with several anti-inflammatories.The objective of this work were to evaluate the chemical investigation of methanolic extract obtained from leaves of D. furfuracea (MEDF) and test the MEDF, such as chloroform (CF), ethyl acetate (EAF) and hydromethanol (HMF) fractions and the alkaloid dicentrinone (DF-1) in vitro antioxidant effects and in vivo models of inflammation.MEDF and CF were analyzed by LC-PDA and the results revealed the presence of alkaloid aporphine and oxoaporphine. The concentrations of total phenols, flavonoids and flavonols were determined. Additionally, MEDF, fractions and dicentrinone were evaluated free radical scavenging activity 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and peroxidation β-carotene/linoleic acid and malondialdehyde (MDA) assays. The anti-inflammatory effects of MEDF, fractions and dicentrinone were studied in carrageenan-induced paw edema. The anti-rheumatic potential was studied in air pouch model and zymosan-induced arthritis.CF fractionation resulted in the isolation of the oxaporphine alkaloid dicentrinone (DF-1). The highest phenols (624.37mg GAE/ g extract), flavonoids (580.51mg QE/ g extract) and flavonols (254.44mg QE/ g extract), concentration was found in extract. In antioxidant tests, MEDF exhibited the highest scavenging activity and lipoperoxidation. The extract (30-300mg/kg) and all tested fractions inhibited the edema induced by carrageenan. The oral administration of DF-1 inhibited both edema associated with carrageenan-induced inflammation in mice. In air pouch model of inflammation, MEDF (30-300mg/kg) and DF-1 (100mg/kg) inhibited leukocyte migration and plasmatic leakage induced by carrageenan in mice. Finally, MEDF (100mg/kg) did not alter zymozan-induced arthritis in mice.The results showed that D. furfuracea exhibits antioxidant, anti-rheumatic potential and anti-inflammatory activity. The presence of the alkaloid dicentrinone in extract and CF fraction could be responsible, at least in part, for the observed effects.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 58-69; https://doi.org/10.1016/j.jep.2017.09.023

Abstract:
Hyptis suaveolens (L) Poit and Boerhavia diffusa Linn are medicinal herbal plants commonly found in the tropics and sub-tropics. They are used to treat various conditions among them boils, dyslipidaemia, eczema, malaria, jaundice and gonorrhoea. Thus, the herbal medicinal extracts are now found as part of some commercial herbal formulations. There has not been adequate characterisation of these medicinal herbs on their effects on drug metabolising enzymes.To investigate the effects of extracts of Hyptis suaveolens (HS) and Boerhavia diffusa (BD) on activity of drug metabolizing enzymes, CYP1A2, CYP2D6 and CYP3A4, as well predict their potential for herb-drug interaction. A secondary aim was to identify constituent compounds such as polyphenolics, in the crude extract preparations of Hyptis suaveolens and Boerhavia diffusa and measure them for activity.CYP450 inhibition assays using recombinant CYP450 (rCYP) and fluorescence screening employing individual isozymes (CYP1A2, CYP2D6 and CYP3A4) were used to determine reversible- and time-dependent inhibition (TDI) profiles of extracts of Hyptis suaveolens and Boerhavia diffusa. Inhibition kinetic parameters, Ki and Kinact were also estimated. UPLC-MS employing a Synapt G2 (ESI negative) coupled to a PDA detector was used to identify polyphenolic compounds in crude extracts of Hyptis suaveolens and Boerhavia diffusa.The inhibitory potency of Hyptis suaveolens and Boerhavia diffusa extracts varied among the different enzymes, with CYP1A2 (3.68 ± 0.10µg/mL) being the least inhibited by HS compared to CYP2D6 (1.39 ± 0.01µg/mL) and CYP3A4 (2.36 ± 0.57µg/mL). BD was most potent on CYP3A4 (7.36 ± 0.94µg/mL) compared to both CYP2D6 (17.79 ± 1.02µg/mL) and CYP1A2 (9.48 ± 0.78µg/mL). Extracts of Hyptis suaveolens and Boerhavia diffusa exhibited TDIs on all CYPs. The most prominent phenolic candidates identified in both medicinal herbs using UPLC-MS analysis included caffeic acid, rutin, quercetin, citric acid, ferulic acid and gluconic acid. These phenolic compounds are thought to potentially give HS and BD their therapeutic effects and inhibitory characteristics affecting CYP450 activities. In vivo predictions showed the potential for HS and BD extracts to cause significant interactions if co-administered with other medications.The study reveals that crude aqueous extracts of HS and BD potentially inhibit drug metabolising isozymes CYP1A2, CYP2D6 and CYP3A4 in a reversible and time-dependent manner. Thus care should be taken when these extracts are co-administered with drugs that are substrates of CYP1A2, CYP2D6 and CYP3A4.
Hsuan-Shu Shen,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 1-8; https://doi.org/10.1016/j.jep.2017.09.025

Abstract:
Patients with lung cancer are frequently treated with Western medical treatments. Recently, patients have begun to use Chinese medicine to strengthen the immune system and alleviate side effects.We aimed to evaluate the association between mortality rate and early use of Chinese herbal products (CHPs) among patients with lung cancer.We conducted a retrospective cohort study based on the National Health Insurance Research Database, Taiwan Cancer Registry, and Cause of Death Data. Patients with newly diagnosed lung cancer between 2002 and 2010 were classified as either the CHP (n = 422) or the non-CHP group (n = 2,828) based on whether they used CHP within 3 months after first diagnosis of lung cancer. A robust Cox regression model was used to examine the hazard ratio (HR) of death for propensity score (PS) matching samples.After PS matching, average survival time of the CHP group was significantly longer than that of the non-CHP group. The adjusted HR (0.82; 95% CI: 0.73-0.92) in the CHP group was lower than the non-CHP group. Stratified by clinical cancer stages, CHP group had longer survival time in stage 3 subgroup. When the exposure period of CHP use was changed from 3 to 6 months, results remained similar (HR = 0.85; 95% CI: 0.76-0.95).Results indicated that patients with lung cancer who used CHP within 3 months after first diagnosis had a lower hazard of death than non-CHP users, especially for stage 3 lung cancer. Further experimental studies are needed to examine the causal relationship.
Martha-Estrella García-Pérez, Alfredo Alfonso-Castillo, Onel Fong Lores, Alexander Batista-Duharte,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 29-37; https://doi.org/10.1016/j.jep.2017.09.022

Abstract:
Petiveria alliacea L. (Phytolaccaceae) is used in folk medicine due to its antispasmodic, diuretic, hypoglycemic, abortive, anti-inflammatory and anticancerogenic properties. Although P. alliacea is considered toxic by people, its toxicity remains a concern since it is strongly dependent on the extraction method and the part of the plant used during tests. Even if some healers prefer to use the aerial parts in a liquefied form or by chewing them, instead of decoctions or infusions, no toxicological studies exist using whole dried stems and leaves.The toxicity of a suspension of the powder from the leaves and stems of P. alliacea was assessed in Sprague Dawley rats by oral administration using two tests: 1) the acute toxic class method, which allows classification of substances according to their intrinsic toxicity and 2) the repeated dose 28-day method, following the guidelines 423 and 407 respectively from the Organization for the Economic Cooperation and Development. Chemical characterization of this powder was performed by GC-MS, UV-fluorescence, proximate and elemental analysis.P. alliacea powder from stems and leaves was classed in the hazard category 5 (LD50>2000 mg/kg) according to the acute toxicology study. There were no toxicity signs at 1000mg/kg in the repeated dose study, although higher values of total leukocytes were found in the satellite and males of the experimental group, which were attributed to the immunomodulatory properties of this plant. According to GC-MS, the prevailing compounds identified were phytol, (R)-(-)-(Z)-14-methyl-8-hexadecen-1-ol, 1-(2-hydrohyethyl)-1,2,4-triazole and methyl β-dimethylaminoisobutyrate. In conclusion, the oral administration of the P. alliacea powder to Sprague Dawley rats did not result in deaths and was not associated with adverse effects reflected in the general condition, body weights or histopathological abnormalities.
Jin Mi Chun, A. Reum Lee, Hyo Seon Kim, Gyo Jeong Gu, ,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 78-88; https://doi.org/10.1016/j.jep.2017.09.006

Abstract:
PJE attenuated allergic airway inflammation by inhibiting Th2 cell activation and macrophage production of inflammatory mediators. Peucedanum japonicum may be candidate therapy for allergic lung inflammation.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 443-468; https://doi.org/10.1016/j.jep.2017.09.007

Abstract:
The current study has an important contribution towards the preservation of indigenous plants' based knowledge. Several plants are carrying important ethnoveterinary uses being practiced by the local people mostly against the gastrointestinal disorders in both regions. Importantly, the cross-cultural approach has reported some new traditional uses of plants against livestock's diseases. Hence, this is an opportunity to investigate such plants phytopharmacologically and toxicologically for the discovery of new drug sources.
You-Chang Oh, Yun Hee Jeong, , ,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 375-383; https://doi.org/10.1016/j.jep.2017.09.010

Abstract:
We confirmed the anti-inflammatory activities and inhibitory mechanism of DH in macrophages and clarified its inhibitory effects in vivo. These findings illustrate the therapeutic potential of DH as a natural anti-inflammatory agent.
Published: 14 September 2017
Journal of ethnopharmacology, Volume 210, pp 477-484; https://doi.org/10.1016/j.jep.2017.09.011

Abstract:
Cedar is part of the phylum of conifers, and it's essential oil has been used for therapeutic purposes since ancient times. In our previous study, we have demonstrated that the inhalation of the Cedrus atlantica essential oil (CaEO) induces an antihyperalgesic effect in a model of postoperative pain. But the mechanism that underlies this effect is not yet fully known.
Zhiqiang Wang, Tiantian Liu, Xiaoping Chen, Hongjie You, Quanbin Zhang, Jingyi Xue, ,
Published: 14 September 2017
Journal of ethnopharmacology, Volume 210, pp 434-442; https://doi.org/10.1016/j.jep.2017.09.014

The publisher has not yet granted permission to display this abstract.
Ibrahim Tümen, , Hakkı Taştan, ,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 211, pp 235-246; https://doi.org/10.1016/j.jep.2017.09.009

Abstract:
Experimental studies shown that P. pinaster's remarkable anti-inflammatory and wound healing activities support the traditional use of the plant, and suggest it could have a place in modern medicine.
Haneul Kim, Hyung Eun Lee, In Ho Jung, Se Jin Jeon, Jiabao Zhang, Yubeen Kwon, Dae Sik Jang,
Published: 14 September 2017
Journal of ethnopharmacology, Volume 211, pp 38-46; https://doi.org/10.1016/j.jep.2017.09.013

Abstract:
The seeds of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F Chow (Rhamnaceae) and the roots of Codonopsis lanceolata (Siedbold & Zucc.) Benth. & Hook. f ex Trautv. (Campanulaceae), contained in the DHP1402, have long been used for treating dementia or hypomnesia as folk medicine.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 469-476; https://doi.org/10.1016/j.jep.2017.09.008

Abstract:
Thistles species (Family: Compositae) are traditionally used in the Mediterranean area, particularly in Sardinia. They are usually gathered from the wild and used for both food and therapeutic purposes, including gastrointestinal disorders.This work aims to evaluate the anti-inflammatory activity of eight wild thistles from Sardinia, in an in vitro model of gastric inflammation, and to identify the major active compounds in the extracts.The hydro-alcoholic extract of the aerial part of each species was prepared. After the induction of inflammation by the addition of tumor necrosis factor-α (TNFα) (10 ng/ml), AGS cells were treated with extracts/pure compounds under study. The inhibition of interleukin-8 (IL-8) release, IL-8 and NF-κB promoter activities and NF-κB nuclear translocation was evaluated. Extracts main components were identified by HPLC-PDA-MS/MS.Only Onopordum horridum Viv. and Onopordum illyricum L. hydro-alcoholic extracts reduced, in a concentration-dependent fashion, the IL-8 release and promoter activity in human gastric epithelial cells AGS. The effect was partially due to the NF-κB pathway impairment. Onopordum hydro-alcoholic extracts were also chemically profiled, and caffeoylquinic acid derivatives were the main compounds identified in the extract. Further investigations showed that 3,5 dicaffeoylquinic acid highly inhibited IL-8 secretion in AGS cells (IC50 0.65μM), thus suggesting that this compound contributed, at least in part, to the anti-inflammatory activity elicited by O. illyricum extracts.Our results suggest that Onopordum species may exert beneficial effects against gastric inflammatory diseases. Thus, these wild plants deserve further investigations as preventive or co-adjuvant agents in gastric diseases.
, Elvira V. De Marco, Olivier Gallo,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 417-433; https://doi.org/10.1016/j.jep.2017.09.005

Abstract:
Headache has been recognized since antiquity. From the late nineteenth to the early to mid-twentieth century, Italian folk remedies to treat headache were documented in a vast corpus of literature sources. The purpose of this paper is to bring to light the plant-based treatments utilized by Italian folk medicine to heal headache in an attempt to discuss these remedies from a modern pharmacological point of view. Moreover, we compare the medical applications described by Hippocrates, Pliny the Elder, Dioscorides, Galen and Serenus Sammonicus with those utilized by Italian folk medicine to check if they result from a sort of continuity of use by over two thousand years. A detailed search of the scientific data banks such as Medline and Scopus was undertaken to uncover recent results concerning the anti-inflammatory, anti-nociceptive and analgesic activities of the plants. Fifty-eight (78.4%) plant-based remedies have shown in vivo, in vitro or in human trials a large spectrum of anti-inflammatory, anti-nociceptive and analgesic activities. Moreover, thirty-one of remedies (41.9%) were already included in the pharmacopoeia between the 5th century BC and the 2nd century AD. Italian folk medicine could be a promising source of knowledge and could provide evidences for active principles that have not as of yet been fully used for their potential.
, Divya Raghavan, Srivani Telapolu, Sarah Kuruvilla, Balakrishna Kedike
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 408-416; https://doi.org/10.1016/j.jep.2017.09.001

Abstract:
Roots of Inula racemosa are used as a cardio protective in Ayurveda in India, being prescribed as a medicine for precordial chest pain, cough and dyspnoea, both singly and as a poly herbal.Evaluation of Phytoestrogenic activity of the root extracts of Inula racemosa and compounds isolated therefrom in vivo, in silico and in vitro.Alcohol (IrA) and hexane (IrH) extracts characterized by HPTLC/GC-MS analysis respectively and processed for compound isolation were evaluated for estrogenic activity (100 &250mg/kg bw) by the Immature rat uterotrophic assay using ethinylestradiol (EE -30µg/kg bw) as standard drug. Alantolactone (ALT), Isoalantolactone (IALT) and Stigmasterolglucoside (SG) isolated from the extracts were characterized and screened in silico for ERα, ERβ binding affinity, assessed in vitro for growth modulatory effects on MCF-7 cells by MTT assay and cell cycle distribution analysis using Flow cytometry. RT-PCR analysis evaluated the mRNA expression of pS2 in these cells post exposure to ALT, IALT and SG.In the IrA treated groups there has been a statistically significant increase (P<0.05) in absolute and normalised uterine weight, uterine diameter, endometrial thickness, luminal epithelial cell height,diameter of ovary and in the number of primary and secondary ovarian follicles relative to untreated controls. Presence of ciliated epithelial cells in the oviduct, elevated number of early growing follicles characterized by an increased oocyte diameter, and signs of vascularization in the cortex of ovarian sections in this group relative to EE treated group are indicative of pervasive activation of follicular growth and initiation. Virtual docking demonstrated ERα affinity for IALT, ERβ affinity for ALT, while SG showed a high binding affinity to both with a relatively greater ERβ binding affinity. Dose dependent decrease in cell viability mediated by IALT and SG in the MTT assay is corroborated by a statistically significant increase (p<0.05) in sub G0-G1 cells by SG at 200 and 400µM in cell cycle analysis and there has been an induction of pS2 by IALT and SG in the ER regulated MCF-7 cells.Demonstration of classical morphological changes induced by estrogen stimulation mediated by IrA in vivo at both the tested doses, isolation of the antioxidant SG from IrA and its dose dependent growth inhibitory effect on estrogen sensitive MCF-7 cells through apoptotic induction and an up regulation of pS2 are suggestive of an anti-estrogenic effect through estrogen receptor binding affinity, typical of phytoestrogens that bind to ER but do not elicit a full estrogenic response. The observed estrogenic effect of IrA suggests a multi mechanistic molecular action involving antioxidant as well as redox signalling pathways acting in consonance with their anti-estrogenic effects owing to the weak estrogen like competitive receptor binding of SG.
Hai Zhang, Yahong Zhao, Zhengxiang Xia, Hongli Du, Yue Gao, Dan Xue, ,
Published: 1 March 2018
Journal of ethnopharmacology, Volume 214, pp 124-133; https://doi.org/10.1016/j.jep.2017.09.003

Abstract:
Myocardial ischemia-reperfusion (I/R) injury is a serious injury that is resulted from the recovery of blood supply after myocardial ischemia. Yangxinshi tablet is a compound Chinese herbal preparation and often used to alleviate the myocardial ischemia in clinical, but its protective mechanism of anti-myocardial ischemia reperfusion injury remains unclear. The objective of this study was to evaluate the anti-I/R injury effect of Yangxinshi tablet on a myocardial I/R rat model and to identify serum biomarker metabolites associated with I/R based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomic method, and explore the metabolic mechanism of anti-I/R injury of Yangxinshi tablet.Unsupervised principle component analysis highlighted significant differences in the metabolome of the myocardial I/R, healthy control and drug-treated rats. Partial least squares-discriminant analysis revealed 25 metabolites as the most potential biomarker metabolites discriminating the myocardial I/R rats and control rats. Most of the metabolites were primarily involved in oxidative stress, energy metabolism, fatty acid metabolism, amino acid metabolism. These metabolites were validated by assessing the efficacy after intragastric administration of Yangxinshit ablet to the myocardial I/R rat model.Based on metabolomic results, the action mechanism of anti-I/R injury of Yangxinshi tablet was concluded as follows: (1) enhance the ability of scavenging free radicals and reactive oxygen species in vivo; (2) provide energy for myocardium via accelerating the intracellular carnitine transportion to accelerate the oxidation of fatty acid and (3) attenuate ceramide to reduce cardiomyocyte apoptosis.Yangxinshi tablet has cardio-protection effects on I/R rats via regulation of multiple metabolic pathways involving in oxidative stress, energy metabolism, fatty acid, and amino acid metabolisms. This study will be meaningful for its clinical application and valuable for further exploring the action mechanism of Yangxinshi tablet.
S. Akhalwaya, , M. Patel
Published: 7 September 2017
Journal of ethnopharmacology, Volume 210, pp 359-371; https://doi.org/10.1016/j.jep.2017.09.002

The publisher has not yet granted permission to display this abstract.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 287-295; https://doi.org/10.1016/j.jep.2017.08.041

Abstract:
The results indicated that these 4 hub target genes, including NR3C2, AR, ESR1 and PGR, might act as potential markers to evaluate the curative effect of GLE treatment in tumor. And, the combined data provide preliminary study of the pharmacological mechanisms of GLE, which may be a promising potential therapeutic and chemopreventative candidate for anti-cancer.
Racquel Oliveira Da Silva Souza, Paloma Leão Sousa, , Tiago Lima Sampaio, Louise Donadello Tessarolo, Francisca Crislandia Oliveira Silva, Maria Gonçalves Pereira,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 311-317; https://doi.org/10.1016/j.jep.2017.08.042

Abstract:
GaEPL showed significant activity against the epimastigote, trypomastigote and amastigote forms of T. cruzi, strain Y, suggesting cell death by necrosis with involvement of reactive oxygen species.
Zhaoyi Wang, Qing Xia, Xin Liu, Wenxue Liu, Wanzhen Huang, Xue Mei, Jun Luo, Mingxu Shan, , , et al.
Published: 1 January 2018
Journal of Ethnopharmacology, Volume 210, pp 318-339; https://doi.org/10.1016/j.jep.2017.08.040

Abstract:
Forsythiae Fructus (called Lianqiao in Chinese), the fruit of Forsythia suspensa (Thunb.) Vahl, is utilized as a common traditional medicine in China, Japan and Korea. It is traditionally used to treat pyrexia, inflammation, gonorrhea, carbuncle and erysipelas. Depending on the different harvest time, Forsythiae Fructus can be classified into two forms, namely Qingqiao and Laoqiao. The greenish fruits that start to ripen are collected as Qingqiao, while the yellow fruits that are fully ripe are collected as Laoqiao. Both are applied to medical use. This review aims to provide a systematic summary of F. suspensa (Forsythia suspensa (Thunb.) Vahl) and to reveal the correlation between the traditional uses and pharmacological activities so as to offer inspiration for future research. All corresponding information about F. suspensa was searched by Scifinder and obtained from scientific databases including Springer, Science Direct, Wiley, Pubmed and China Knowledge Resource Integrated (CNKI). Local dissertations and books were searched as well. According to classical Chinese herbal texts and Chinese Pharmacopoeia, Forsythiae Fructus dominantly displays heat-clearing and detoxifying effects in TCM prescriptions. In modern research, more than 230 compounds were separated and identified from F. suspensa. 211 Of them were isolated from fruits. Lignans and phenylethanoid glycosides are considered as the characteristic and active constituents of this herb, such as forsythiaside, phillyrin, rutin and phillygenin. They exhibited anti-inflammatory, antioxidant, antibacterial, anti-virus, anti-cancer and anti-allergy effects, etc. Currently, there is no report on the toxicity of Forsythiae Fructus, despite slight toxicity of forsythiaside reported in local publications. Compared to Laoqiao, Qingqiao contains higher levels of forsythiaside, forsythoside C, cornoside, rutin, phillyrin, gallic acid and chlorogenic acid and lower levels of rengyol, β-glucose and S-suspensaside methyl ether. Heat-clearing actions of Forsythiae Fructus are based on the anti-inflammatory and antioxidant properties of lignans and phenylethanoid glycosides. Detoxifying effects attribute to the antibacterial, antiviral and anti-cancer activities of Forsythiae Fructus. And traditional Chinese medicine (TCM) characteristics of Forsythiae Fructus (bitter flavor, slightly cold nature and lung meridian) supported its strong anti-inflammatory effects. In addition, the remarkable anti-inflammatory and antioxidant capacities of Forsythiae Fructus contribute to its anti-cancer and neuroprotective activities. The higher proportion of lignans and phenylethanoid glycosides in Qingqiao than Laoqiao might explain the better antioxidant ability of Qingqiao and more frequent uses of Qingqiao in TCM prescriptions. For future research, more in vivo experiments and clinical studies are encouraged to further clarify the relation between traditional uses and modern applications. Regarding to Qingqiao and Laoqiao, they remain to be differentiated by all-round quality control methods, and the chemical compositions and clinical effects between them should be compared.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 372-385; https://doi.org/10.1016/j.jep.2017.08.039

Abstract:
In the Peruvian Amazon, the use of medicinal plants is a common practice. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point for this work was a set of interviews of people living in rural communities from the Peruvian Amazon about their uses of plants. Protozoan diseases are a public health issue in the Amazonian communities, who partly cope with it by using traditional remedies. Validation of these traditional practices contributes to public health care efficiency and may help identify new antiprotozoal compounds. to inventory and validate the use of medicinal plants by rural people of Loreto region. Rural mestizos were interviewed about traditional medication of parasite infections with medicinal plants. Ethnopharmacological surveys were undertaken in two villages along Iquitos-Nauta road (Loreto region, Peru), namely 13 de Febrero and El Dorado communities. Forty-six plants were collected according to their traditional use for the treatment of parasitic diseases, 50 ethanolic extracts (different parts for some of the plants) were tested in vitro on Plasmodium falciparum (3D7 sensitive strain and W2 chloroquine resistant strain), Leishmania donovani LV9 strain and Trypanosoma brucei gambiense. Cytotoxic assessment (HUVEC cells) of the active extracts was performed. Two of the most active plants were submitted to preliminary bioguided fractionation to ascertain and explore their activities. From the initial plants list, 10 were found to be active on P. falciparum, 15 on L. donovani and 2 on the three parasites. The ethanolic extract from Costus curvibracteatus (Costaceae) leaves and Grias neuberthii (Lecythidaceae) bark showed strong in vitro activity on P. falciparum (sensitive and resistant strain) and L. donovani and moderate activity on T. brucei gambiense. The Amazonian forest communities in Peru represents a source of knowledge on the use of medicinal plants. In this work, several extracts with antiprotozoal activity were identified. This work contributes to validate some traditional uses and opens subsequent investigations on active compounds isolation and identification.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 179-191; https://doi.org/10.1016/j.jep.2017.08.021

Abstract:
Sijunzi decoction (SJZD) is a well known traditional Chinese prescription used for the treatment of gastrointestinal disorders and immunity enhancement. It has been found to indeed improve life quality of chemotherapy patients and extensive used in clinical conbined with chemotherapeutics for the treatment of cancer.The aim of this study was to investigate the preventive effect of the immunotoxicity of SJZD on mitomycin C (MMC) and the metabolic mechanism of action.NMR and MS-based metabolomics approaches were combined for monitoring MMC-induced immunotoxicity and the protective effect of SJZD. Body weight change and mortality, histopathological observations and relative viscera weight determinations of spleen and thymus, sternum micronucleus assay and hematological analysis were used to confirm the immunotoxicity and attenuation effects. An OPLS-DA approach was used to screen potential biomarkers of immunotoxicity and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathways.8 biomarkers in plasma samples, 19 in urine samples and 10 in spleen samples were identified as being primarily involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. The most critical pathway was alanine, aspartate and glutamate metabolism.The variations in biomarkers revealed the preventive effect of the immunotoxicity of SJZD on MMC and significant for speculating the possible metabolic mechanism.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 296-310; https://doi.org/10.1016/j.jep.2017.08.035

Abstract:
The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis L. (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported.This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research.Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017.EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated hemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant).EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed.
, , Qi Wang, , Feng Zhang, Jing-Zhen Shi, Cen Li, M. George Cherian
Published: 1 January 2018
Journal of Ethnopharmacology, Volume 210, pp 340-350; https://doi.org/10.1016/j.jep.2017.08.037

Abstract:
Herbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries.This review uses cinnabar (HgS) and realgar (As4S4) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives.A literature search on cinnabar and realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out. Traditional medicines containing both cinnabar and realgar (An-Gong-Niu-Huang Wan, Hua-Feng-Dan); mainly cinnabar (Zhu-Sha-An-Shen Wan; Zuotai and Dangzuo), and mainly realgar (Huang-Dai Pian; Liu-Shen Wan; Niu-Huang-Jie-Du) are discussed.Both cinnabar and realgar used in traditional medicines are subjected to special preparation procedures to remove impurities. Metals in these traditional medicines are in the sulfide forms which are different from environmental mercurials (HgCl2, MeHg) or arsenicals (NaAsO2, NaH2AsO4). Cinnabar and/or realgar are seldom used alone, but rather as mixtures with herbs and/or animal products in traditional medicines. Advanced technologies are now used to characterize these preparations. The bioaccessibility, absorption, distribution, metabolism and elimination of these herbo-metallic preparations are different from environmental metals. The rationale of including metals in traditional remedies and their interactions with drugs need to be justified. At higher therapeutic doses, balance of the benefits and risks is critical. Surveillance of patients using these herbo-metallic preparations is desired.Chemical forms of mercury and arsenic are a major determinant of their disposition, efficacy and toxicity, and the use of total Hg and As alone for risk assessment of metals in traditional medicines is insufficient.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 39-46; https://doi.org/10.1016/j.jep.2017.08.027

Abstract:
Fritillariae Bulbus (Beimu in Chinese) is derived from the bulbus of many Fritillaria species (family Liliaceae), which has been used as an antitussive herb in traditional Chinese medicine for more than 2000 years. Due to the complexity of plant origins and significant variations in chemical profiles, the characterization of the profile of the major bioactive constituents and its association with pharmacological activity are important for the quality control of Beimu herbs from different origins.This study aims to investigate the distribution of major bioactive isosteroidal alkaloids in Beimu herbs of different origins and its correlation with the tracheobronchial relaxant activity.Quantification of 7 main bioactive 5α-cevanine isosteroidal alkaloids, including ebeiedine, ebeiedinone, hupehenine, isoverticine, verticine, verticinone and imperialine, in 23 Fritillaria species was performed using gas chromatography. The relaxant effect of different extracts of 4 commonly used Beimu herbs, namely Zhe-Beimu (F. thunbergii Miq.), Chuan-Beimu (F. cirrhosa D. Don), Hubei-Beimu (F. hupehensis Hsiao et K. C. Hsia) and Yi-Beimu (F. pallidiflora Schrenk), was evaluated using rat isolated tracheal and bronchial preparations pre-contracted with carbachol, the well established in vitro antitussive model.Amongst 23 Fritillaria species detected, significant variations of the types and quantities of 7 major isosteroidal alkaloids were determined, which served as an important indicator for the classification of different Beimu herbs with distinct geographic distributions. Based on the type and quantity of these alkaloids, different origins of Beimu could be clearly clustered into several subgroups by principal component analysis. Furthermore, both crude alkaloid and water extracts of all 4 Beimu herbs showed a dose-dependent tracheobronchial relaxation with different potencies. The total content of alkaloids (weight adjusted based on the activity of individual alkaloids) in Beimu extracts significantly correlated with their tracheobronchial relaxation effects (r(2)>0.9, p<0.001).The results demonstrated that the differences in chemical profile of major bioactive isosteroidal alkaloids and pharmacological activity of Beimu could be incorporated into a simple and unified method for quality control and potential prediction of activity of Beimu herbs from different origins.
Ai-Ling Li, Bang-Jiao Chen, , Ming-Xing Zhou, Yan-Ru Li, Dong-Mei Ren, , ,
Published: 1 January 2018
Journal of Ethnopharmacology, Volume 210, pp 260-274; https://doi.org/10.1016/j.jep.2017.08.022

Abstract:
The calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino (Physalis Calyx seu Fructus), have been widely used in traditional and indigenous Chinese medicines for the therapy of cough, excessive phlegm, pharyngitis, sore throat, dysuria, pemphigus, eczema, and jaundice with a long history. The present review aims to achieve a comprehensive and up-to-date investigation in ethnomedical uses, phytochemistry, pharmacology, and toxicity of P. alkekengi var. franchetii, particularly its calyxes and fruits. Through analysis of these findings, evidences supporting their applications in ethnomedicines are illustrated. Possible perspectives and opportunities for the future research are analyzed to highlight the gaps in our knowledge that deserves further investigation. Information on P. alkekengi var. franchetii was collected via electronic search of major scientific databases (e.g. Web of Science, SciFinder, Google Scholar, Pubmed, Elsevier, SpringerLink, Wiley online and China Knowledge Resource Integrated) for publications on this medicinal plant. Information was also obtained from local classic herbal literature on ethnopharmacology. About 124 chemical ingredients have been characterized from different parts of this plant. Steroids (particularly physalins) and flavonoids are the major characteristic and bioactive constituents. The crude extracts and the isolated compounds have demonstrated various in vitro and in vivo pharmacological functions, such as anti-inflammation, inhibition of tumor cell proliferation, antimicrobial activity, diuretic effect, anti-diabetes, anti-asthma, immunomodulation, and anti-oxidation. P. alkekengi var. franchetii is an important medicinal plant for the ethnomedical therapy of microbial infection, inflammation, and respiratory diseases (e.g. cough, excessive phlegm, pharyngitis). Phytochemical and pharmacological investigations of this plant definitely increased in the past half century. The chemical profiles, including ingredients and structures, have been adequately verified. Modern pharmacological studies supported its uses in the traditional and folk medicines, however, the molecular mechanisms of purified compounds remained unclear and were worth of further exploration. Therefore, the researchers should be paid more attention to a better utilization of this plant.
, Fang Dong, Guangquan Li, , Congen Zhang, Yanzhong Han, Lanzhi He, Ping Yin, Bin Wang, Xiuxiu Sang, et al.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 232-241; https://doi.org/10.1016/j.jep.2017.08.029

Abstract:
Liuweiwuling (LWWL) tablets contain a six-herb Chinese formula and are commonly prescribed to facilitate nourishment of the liver and kidneys, clear away toxic materials and activate blood circulation. Administration of LWWL is well known for its protective effects on the liver and its capacity to confer long-term stability in patients exhibiting reduced transaminase levels. Clinical studies have reported that LWWL can also be used for the treatment of liver fibrosis with associated treatment regimens resulting in a concomitant reduction in transforming growth factor β1 (TGF-β1) levels in the serum of patients with hepatic fibrosis. TGF-β1 plays a prominent role in stimulating liver fibrogenesis and this effect is mediated by myofibroblasts (MFB) derived from hepatic stellate cells (HSCs). It is likely that this phenomenon underpins the antifibrotic effects associated with LWWL.The purpose of this study was to investigate the antifibrotic effects and mechanisms pertaining to LWWL.Hepatic fibrosis was induced in rats following bile duct ligation (BDL). Rats that underwent BDL received daily gavage administration of colchicine (0.2mg/kg per day), LWWL (0.4, 1.6, 6.4g/kg per day) or PBS (for the control group). Pathological changes in hepatic tissue were examined using hematoxylin and eosin (HE) and sirius red staining. Immunohistochemical analysis was performed to monitor α-SMA and type I collagen (Collagen I) protein expression. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot analyses were used to monitor the expression of genes and proteins in the TGF-β/Smad signaling pathway, including TGF-β1, bone morphogenic protein and activin membrane-bound inhibitor (Bambi), Smad3, phosphorylated Smad3 (p-Smad3) and Smad7. We also monitored the expression of genes and proteins in the nuclear factor-κB (NF-κB) signaling pathway, including NF-κB p65, IκBα and phosphorylation of IκBα (p-IκBα), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1β (IL-1β).LWWL dose-dependently inhibited BDL-induced liver injury and hepatic fibrosis in rats. Furthermore, LWWL reduced liver tissue collagen deposition, hydroxyproline content, liver dysfunction and α-SMA expression in BDL-induced hepatic fibrosis rats. Moreover, LWWL markedly prevented activation of the TGF-β/Smad signaling pathway by inhibiting expression of Smad2/3 and phosphorylation of Smad3, and upregulating the expression of Bambi and Smad7. In addition, LWWL regulated the expression of the inflammatory cytokines IL-1β, TNF-α and IL-6 by inhibiting the activation of NF-κB p65 and the phosphorylation of IκBα, and increasing the expression of IκBα.LWWL can attenuate BDL-induced hepatic fibrosis in rats, and this effect may be due to modulation of the NF-κB-dependent inflammatory response and activation of HSC and TGF-β/Smad-mediated synthesis and degradation of Collagen I.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 254-259; https://doi.org/10.1016/j.jep.2017.08.038

Abstract:
Artemisia annua has been used for > 2000yrs to treat fever and is more recently known for producing the important antimalarial drug, artemisinin. Artemisinin combination therapies (ACTs) are effective for treating malaria, but are often unavailable to those in need. Dried leaves of A. annua (DLA) have recently been studied as a cost effective alternative to traditional ACTs. DLA was shown to dramatically increase oral bioavailability compared to pure artemisinin, so more investigation into the mechanisms causing this increased bioavailability is needed. In this study, we used a simulated digestion system coupled with Caco-2 cell permeability assays to investigate the intestinal permeability of DLA compared to pure artemisinin. We also determined the effects of different phytochemicals (7 flavonoids, 3 monoterpenes, 2 phenolic acids, scopoletin and inulin) and the cytochrome P450 isoform CYP3A4 on artemisinin intestinal permeability. Artemisinin permeability, when delivered as digested DLA, significantly increased by 37% (Papp = 8.03 × 10-5cms-1) compared to pure artemisinin (Papp = 5.03 × 10-5cms-1). However, none of the phytochemicals tested or CYP3A4 had any significant effect on the intestinal permeability of artemisinin. We also showed that essential oil derived from A. annua negatively affected the intestinal permeability of artemisinin, but only after simulated digestion. Finally, we showed that A. annua essential oil reduced the transepithelial electrical resistance of Caco-2 monolayers, but only in the presence of bile. Although also reduced by essential oils, artemisinin Papp subsequently recovered in the presence of plant matrix. These results shed light on the mechanisms by which DLA enhances the oral bioavailability of artemisinin.
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 275-286; https://doi.org/10.1016/j.jep.2017.08.036

Abstract:
The present study revealed the potentials of A. nilotica to alleviate diabetes-related systemic complications by limiting oxidative stress which justified the ethnopharmacological antidiabetic claim.
Yi-Hong Zou, Liang Zhao, You-Kai Xu, Jing-Mei Bao, Xin Liu, Jun-Sheng Zhang, Wei Li, Abrar Ahmed, Sheng Yin,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 95-106; https://doi.org/10.1016/j.jep.2017.08.034

Abstract:
Salvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history.The aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases.The aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C18, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-α) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-κB and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay.Six new (1-6, salviplenoids A-F) and ten known (7-16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB and Erk1/2.Among all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-κB and Erk1/2 signaling pathways.
Matheus M. dos Santos, , Gabriel T. de Macedo, , , Aline A. Boligon, Diego Souza, , João B.T. da Rocha,
Published: 1 January 2018
Journal of ethnopharmacology, Volume 210, pp 69-79; https://doi.org/10.1016/j.jep.2017.08.033

Abstract:
Syzygium cumini (L.) Skeels is a plant widely used in folk medicine to treat diabetes mellitus (DM). The tea from its leaves is frequently used by diabetics for lowering hyperglycemia. There is a close relationship between DM and atherosclerosis, a chronic immuno-inflammatory disease, were the early stages encompass oxidative and glycative modifications in the structure of low density lipoprotein (LDL).To investigate the potential protective effects of aqueous-leaf extract from Syzygium cumini (S.cExt) against CuSO4-induced oxidation and methylglyoxal (MG)-induced glycation of human LDL in vitro.LDL oxidative changes were evaluated by measuring conjugated dienes (CD) formation, thiobarbituric acid reactive substances (TBARS) levels, quenching of tryptophan (Trp) fluorescence and structural modifications in LDL particle. In LDL glycated by MG (glyLDL), we determined the levels of fluorescent advanced glycation end products (AGEs) and mobility by agarose gel electrophoresis.S.cExt blocked oxidative events induced by CuSO4 in human LDL, plasma and serum. Fourier transform infrared spectroscopy (FT-IR) revealed that specific regions of ApoB100 were oxidized by CuSO4 in human LDL and that S.cExt reduced these oxidations. Unlike, the increased AGEs levels and eletrophoretic mobility observed in LDL MG-glycated were not modified by S.cExt.The findings herein indicate that S.cExt could be tested in atherogenesis models as potential protective agent against LDL oxidation.
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