Srolo Bzhtang, a traditional Tibetan medicine formula, inhibits cigarette smoke induced airway inflammation and muc5ac hypersecretion via suppressing IL-13/STAT6 signaling pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Srolo Bzhtang (SBT), a traditional Tibetan medicine formula, was composed of three herbs, Solms-Laubachia eurycarpa, Bergenia purpurascens, Glycyrrhiza uralensis, and one lac, and was first documented in the ancient Tibetan medical work Four Medical Tantras (rGyud-bzhi) in the eighth century AD. It has been widely used to treat lung "phlegm-heat" syndromes such as chronic bronchitis and chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of this study was to evaluate the potential influences of aqueous extract of SBT on airway inflammation and mucus secretion and to reveal the underlying mechanism in a rat model of cigarette smoke (CS)-induced chronic bronchitis (CB). MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were randomly divided to six groups: control (room air exposure), model (CS exposure), DEX (CS exposure and 0.2 mg/kg/day dexamethasone), and three SBT (CS exposure and 1.67, 2.50, and 3.34 g/kg/day SBT) groups. DEX and the three doses of SBT were administered by oral gavage every day for eight weeks. Pathological changes and mucus expression in the lung tissue were determined by hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff (AB-PAS) and immunohistochemical staining. The levels of cytokines in bronchoalveolar lavage fluid (BALF) were assessed by ELISA. Western blot analysis and qRT-PCR were performed to explore the effects of SBT on the expression of IL-13, STAT6 and MUC5AC. RESULTS: Pretreatment with SBT attenuated the TNF-α, IL-8, IL-13 expression levels in BALF and the inflammatory cell infiltration in bronchial walls and peribronchial lung tissue. SBT exhibited a dose-dependent downregulation of MUC5AC expression as assessed by AB-PAS and immunohistochemical staining. The protein and mRNA levels of IL-13, STAT6/p-STAT6 and MUC5AC were also downregulated by SBT preconditioning. CONCLUSION: These results for the first time demonstrated that SBT exhibited protective effects on CS-induced airway inflammation and MUC5AC hypersecretion, which might be related to the downregulation of the IL-13/STAT6 signaling pathway.

Antianxiety activity guided isolation and characterization of bergenin from Caesalpinia digyna Rottler roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia digyna Rottler (Caesalpiniaceae) roots have been used traditionally for soothing nerves, as nervine tonic and febrifuge. The aim of the present study was to isolate the antianxiety constituent(s) from C. digyna roots following bioactivity guided fractionation approach. MATERIAL AND METHODS: Bioactive fraction F4 was subjected to column chromatography to get three sub-fractions (F4.1-F4.3) and a compound CD2. CD1 and CD2 were characterized using standard spectral techniques. Three fractions (F4.1-F4.3) were evaluated for antianxiety activity in mice using EPM. An effective dose of the antianxiety principle was optimized, and its activity was, further evaluated using open field and mirror chamber tests. RESULTS: CD1 and CD2 characterized as bergenin, exhibited significant antianxiety activity at 80mg/kg, po which was statistically comparable to that of diazepam (2mg/kg, po). However, F4.1-F4.3 were observed to be devoid of antianxiety activity. Bergenin also exhibited significant antianxiety activity in open field and mirrored chamber tests. CONCLUSIONS: Bergenin, isolated from roots of C. digyna, exhibits significant antianxiety activity at 80mg/kg, po in three different models for evaluating antianxiety activity. This activity of bergenin is being reported for the first time.

The natural product bergenin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting NF-kappaB activition.

ETHNOPHARMACOLOGICAL RELEVANCE: Bergenin, an active constituent of the plants of the genus Bergenia, was reported to have anti-inflammatory effects in the treatment of chronic bronchitis and chronic gastritis clinically. However, its therapeutic effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its potential mechanisms of actions were still unknown. AIM OF THIS STUDY: To evaluate the effect of bergenin on murine model of acute lung injury induced by LPS and also to explore its potential mechanisms. MATERIALS AND METHODS: Half an hour and 12h after an intranasal inhalation of LPS, male BALB/c mice were treated with bergenin (50,100 and 200mg/kg) or dexamethasone (DEX, 5mg/kg) by gavage. Twenty-four hours after LPS exposure, the lung wet/dry ratio, histological changes, myeloperoxidase (MPO) in lung tissues, inflammatory cells (in BALF) and cytokines (in BALF and serum) were detected. Meanwhile, the protein expression of MyD88 and the phosphorylation of NF-κB p65 in lung tissue were analyzed using immunoblot analysis. Moreover, the nuclear translocation and the phosphorylation of NF-κB p65 in Raw264.7 cells were also analyzed. The viability of Raw264.7 cells was determined by MTT assay. RESULTS: Results showed that bergenin significantly decreased pulmonary edema, improved histological changes and reduced MPO activity in lung tissues. Moreover, bergenin obviously decreased inflammatory cells, IL-1ß and IL-6 production in BALF, as well as IL-1ß, TNF-α and IL-6 production in serum of LPS-induced ALI mice. Furthermore, bergenin markedly inhibited LPS-induced NF-κB p65 phosphorylation, as well as the expression of MyD88 but not the expression of NF-κB p65 in lung tissues. Additionally, bergenin also significantly inhibited the nuclear translocation and the phosphorylation of NF-κB p65 stimulated by LPS in Raw264.7 cells. CONCLUSIONS: These findings suggested that bergenin had a therapeutic effect on LPS-induced ALI by inhibiting NF-κB activition.

Immuno-enhancement effects of Yifei Tongluo Granules on cyclophosphamide-induced immunosuppression in Balb/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Yifei Tongluo Granules has been employed clinically with the combination of chemotherapy agents to treat patients with multidrug-resistant tuberculosis. However, the mechanisms underlying the therapeutic potential have not been well elucidated. The present study was employed to verify immunomodulatory effect and to investigate the underlying mechanisms which have not been explored. MATERIALS AND METHODS: The study samples of total extracts (FB-E) and polysaccharides (FB-P) were prepared by the extraction of the Yifei Tongluo Granules using appropriate techniques. A simple immunodeficient mice model was established by challenging Balb/c mice with cyclophosphamide in order to avoid the handling of tuberculosis viruses. The in vivo study was thus designed to systematically elucidate the immuno-enhancement effects of Yifei Tongluo Granules extracts in immunosuppressed mice induced by cyclophosphamide. Balb/c mice were orally ingested once daily with the low and high doses of two different extracts for ten consecutive days, respectively, accompanied by intraperitoneal injection of cyclophosphamide (60mg/kg) on days 1-3 and 10. RESULTS: Compared with the model group, the treatment of immunodeficient mice with the low and high doses of the extracts FB-E or FB-P enhanced spleen and thymus indices, T- and B-cell proliferation as well as increased the activities of splenic natural killer, lymphokine activated killer, cytotoxic T lymphocyte cells and peritoneal macrophage phagocytosis. In addition, the FB-E or FB-P treatment balanced the ratio of Th1/Th2 and up-regulated the CD4+/CD8+ ratio in the serum. CONCLUSIONS: These results demonstrate, for the first time, that the treatment of the cyclophosphamide-challenged mice with the Yifei Tongluo Granules extracts resulted in accelerated recovery of immunosuppression, sugguesting that the immunomodulation might be the mechanism for the observed clinical benefits of Yifei Tongluo Granules. Our findings provide preliminary mechanistic study evidences for clinical application of Yifei Tongluo Granules in patients with immunodeficient diseases such as tuberculosis.

Diversity, pharmacology and synthesis of bergenin and its derivatives: potential materials for therapeutic usages.

Bergenin, a natural secondary metabolite, has been isolated from different parts of a number of plants. It is one of active ingredients in herbal and Ayurvedic formulations. It exhibits antiviral, antifungal, antitussive, antiplasmodial, antiinflammatory, antihepatotoxic, antiarrhythmic, antitumor, antiulcerogenic, antidiabetic and wound healing properties. It has been analyzed and estimated in different plant extracts, blood and drug samples using chromatographic techniques, and pharmacokinetic studies have been made. Several bergenin derivatives were isolated and/or synthesized and were found to possess pharmacological activities. Total synthesis of bergenin and its derivatives were reported. This review article covers literature on bergenin and its derivatives until 2013. Ethnomedicinal value of bergenin containing plant materials is also highlighted. This comprehensive review provides information on the potentiality of bergenin and its derivatives for therapeutic usages.

Bioactive phloroglucinols from Mallotus oppositifolius.

The two new acylphloroglucinol derivatives, methylene-bis-aspidinol AB (1) and mallopposinol (2), together with the nine known compounds, aspidinol B (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of Mallotus oppositifolius. Their structures were elucidated by spectral analysis including MS, 1D and 2D-NMR spectroscopy. In vitro trypanocidal and antileishmanial activities of compounds 1-9 were evaluated. Mallopposinol (2) and aspidinol B (3) displayed weak antileishmanial activities against Leishmania donovani promastigotes, with EC50 values of 21.3 and 38.8µM, respectively. Only the methylene-bis-aspidinol (4) exhibited trypanocidal activity against Trypanosoma brucei brucei trypomastigotes (LC100=0.8µM) similar to the reference drug pentamidine (LC100=0.4µM).