Preventive effect of Ya'an Tibetan tea on obesity in rats fed with a hypercaloric high-fat diet revealed by gut microbiology and metabolomics studies.

Ya'an Tibetan Tea (YATT) is a classic dark tea variety fermented with a unique geographical environment and traditional craftsmanship. Previous research indicates that it is beneficial for obesity and related metabolic disorders, but no systematic research currently reveals its precise mechanisms. This work investigated the preventive effect of YATT on obesity and the corresponding potential mechanisms by performing 16S rRNA gene sequencing and metabolomics studies. Our results demonstrated that YATT could significantly improve the body weight and fat deposition in hypercaloric high-fat diet (HFD)-induced obese rats, enhance antioxidant enzymes activity and reduce inflammation, and reverse the liver damage caused by an HFD. Moreover, 16S rRNA analysis showed that YATT could improve the intestinal microbial disorders caused by the HFD by significantly reversing the increase in Firmicutes/Bacteroidetes（F/B）ratio and the relative abundance of flora associated with the HFD, such as unclassified_Lachnospiraceae and Romboutsia flora. In addition, metabolomic analysis of cecum contents identified 121 differential metabolites, of which 19 were common to all experimental rats fed with and without a high-fat diet. Strikingly, 17 of the most prevalent 19 differential metabolites, including Theobromine, L-Valine, and Diisobutyl phthalate, were considerably reversed by YATT. Enrichment analysis of the metabolic pathways of these differential metabolites indicated that Caffeine metabolism, Phenylalanine metabolism, and Lysine degradation are the potential metabolic pathways responsible for the obesity prevention effect of YATT. Collectively, this work revealed that YATT has good potential for obesity prevention and the improvement of intestinal microbial communities, potentially due to the YATT-induced alterations in the metabolic pathways and functional metabolite levels of caffeine and amino acids. These results inform the material basis of YATT for obesity prevention and its mechanisms and provide essential insights for developing YATT as a healthy beverage for obesity prevention.

Combinations of Tibetan tea and medicine food homology herbs: A new strategy for obesity prevention.

Obesity has become a significant global public health problem. Functional drinks have been an essential direction for obesity prevention research. The present study investigated the preventive effect and safety of winter melon and lotus leaf Tibetan tea (WLTT, a compound tea drink based on Ya'an Tibetan Tea and medicine food homology herbs) on obesity. The rats' hypercaloric high-fat diet (HFD) obesity model was established to evaluate obesity prevention and explored the mechanism through intestinal flora regulation. The results showed that in obese rats with the intervention of WLTT (400, 800, and 1600 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels, and antioxidant enzyme activity (SOD, GSH-Px, and MDA) were progressively improved. 16S rRNA high-throughput sequencing showed that WLTT could improve intestinal flora disorders due to HFD, which significantly reversed the relative abundance of Firmicutes and the F/B ratio associated with an HFD, and significantly upregulated the relative abundance of Verrucomicrobia. At the genus level, the downregulation of the relative abundance of Akkermansia and unclassified_Lachnospiraceae groups, and the upregulation of the relative abundance of Romboutsia, Ruminococcus, Corynebacteriume, and Saccharibacteria_genera_incertae_sedis groups brought about by the HFD were significantly reversed. The results of the above experiments were compared favorably with those of a parallel experiment with Bi -Sheng -Yuan slimming tea (BSY, a functional drink based on green tea and medicine food homology herbs). Overall, the findings have provided that WLTT can prevent obesity owing to an HFD by regulating intestinal flora and has a good safety profile, and combinations of Tibetan tea and medicine food homology herbs could be a new option for obesity prevention.

Dendrobium nobile Lindl. Polysaccharides protect fibroblasts against UVA-induced photoaging via JNK/c-Jun/MMPs pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl. is an orchid species that is found throughout Asia, including Thailand, Laos, Vietnam, and China. It has been used to treat tumors, hyperglycemia, hyperlipidemia, and neurological disorders caused by aging in recent decades. AIM OF THE STUDY: To investigate the antagonistic effect of Dendrobium nobile Lindl. Polysaccharides (DNLP) on UVA-induced photoaging of Human foreskin fibroblasts (HFF-1) and explore its possible anti-aging mechanisms. MATERIALS AND METHODS: An in vitro photoaging model of dermal fibroblasts was established with multiple UVA irradiations. Fibroblasts were treated with 0.06 mg/ml, 0.18 mg/ml, 0.54 mg/ml of DNLP one day before photodamage induction. The levels of reactive oxygen species (ROS), Malondialdehyde (MDA), cell viability and longevity, Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GSH-Px) enzymatic activities were determined. We examined how DNLP ameliorates the effects of photoaging, the JNK/c-Fos/c-Jun pathway, senescence-associated ß-galactosidase (SA-ß-Gal), and MMP expression levels were measured. RESULTS: UVA irradiation reduced the viability, lifespan, and proliferation of HFF-1 cells, increased ROS and lipid peroxidation and decreased the activities of free radical scavenging enzyme systems SOD, CAT, and GSH-Px. DNLP treatment can reverse UVA damage, reduce SA-ß-Gal expression, reduce phosphorylation activation of the JNK/c-Fos/c-Jun pathway and inhibit MMP-1, MMP-2 MMP-3, and MMP-9 protein expression. CONCLUSIONS: DNLP can effectively inhibit UVA damage to HFF-1 and prevent cell senescence. Its mechanism of action may increase antioxidant enzyme activity while inhibiting JNK pathway activation and MMPs expression.

Preparation and Safety Evaluation of Centella asiatica Total Glycosides Nitric Oxide Gel and Its Therapeutic Effect on Diabetic Cutaneous Ulcers.

Diabetic cutaneous ulcers (DCU) are a chronic and refractory complication of diabetes mellitus, which can lead to amputation or even death in extreme cases. Promoting the early healing of DCU and reducing the disability rate and treatment cost are important research topics in treating with integrated traditional Chinese and Western medicine. Centella asiatica total glycosides are extracted from the traditional Chinese medicine Centella asiatica and have angiogenic, anticancer, antioxidant, and wound healing effects. Nitric oxide (NO) is a critical component of wound healing. During the development of DCU, endogenous NO secretion is insufficient. It has been reported that exogenous nitric oxide can promote wound healing, but it is difficult to adhere to the skin because of its short half-life. Therefore, in this study, we used the polymer excipient hydroxyethyl cellulose as the matrix, combined with Centella asiatica total glycosides and NO, and developed a new type of topical gel that can promote wound healing. At the same time, we made a comprehensive research and evaluation on the preparation technology, quality standard, skin toxicity, reproductive toxicity, and pharmacodynamics against diabetic skin ulcers of the gel. According to our research results, the combination of Centella asiatica total glycosides and nitric oxide can accelerate the healing speed of DCU wounds, and 8% Centella asiatica total glycosides nitric oxide gel (CATGNOG) has the best effect in ulcer wound healing. CATGNOG has the advantages of feasible preparation method, controllable quality, good stability at low temperature, and no apparent skin toxicity and reproductive toxicity. It can effectively inhibit the growth of bacteria on the wound surface, relieve the inflammatory reaction of the wound surface, and promote the healing of ulcer wound, which provides a basis for further research of the preparation in the future.

Anti-aging properties of Dendrobium nobile Lindl.: From molecular mechanisms to potential treatments.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium Nobile Lindl. (DNL) is one of the central herbs in traditional Chinese medicine which mainly distributes in Guizhou, Yunnan, Guangxi and other sub-tropical areas south of the Yangtze River. In the past decades, it has been used to treat tumors, hyperglycemia, hyperlipidemia, and diseases of the nervous system that may be caused by aging. AIM OF THE REVIEW: The purpose of this review is to summarize the anti-aging information of DNL from the molecular mechanism level, including classic theories related to aging, main chemical components, pharmacological research and anti-aging theory based on traditional Chinese medicine theory, for exploring the future development and clinical treatment. MATERIALS AND METHODS: The information in this paper has been collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, Ph.D. and M.S. dissertations systematically. RESULTS: In this paper, we have reviewed the several mechanisms underlying the potential effects of DNL on the prevention of aging, including the scavenging of free radicals for oxidation, delaying of DNA impairment, inhibition of apoptosis, and alteration of DNA methylation. Together with the theory of telomeres, this review also has summarized recent research progress in the use of DNL and its traditional efficacy. CONCLUSIONS: We conclude that "strengthening Yin and benefiting the spirit", "thickening the intestine and stomach", "lightning the body and prolonging the life-span", and delaying aging, are key effects of DNL that can be used to combat age-related diseases (ARDs) such as Alzheimer's disease, hyperlipidemia, and diabetes. This review provides a reference for future study of ARDs and the clinical application of DNL.

Asiaticoside nitric oxide gel accelerates diabetic cutaneous ulcers healing by activating Wnt/ß-catenin signaling pathway.

Diabetic ulcers, gangrene, local infections and other traumatic symptoms of wound healing are all directly related. Promoting the early healing of diabetic cutaneous ulcers (DCU) and reducing the disability and treatment costs is an important research project integrating traditional Chinese and Western medicine. Nitric oxide (NO) is a key component of wound healing, and endogenous NO secretion is insufficient during the development of DCU. It has been reported that exogenous NO can promote wound healing, but exogenous NO has a short half-life and is difficult to adhere to the skin. Asiaticoside (AC) is extracted from the traditional Chinese medicine Centella asiatica, and has angiogenic, anticancer, antioxidant, anti-inflammatory, and wound-healing effects. Therefore, our study is based on the hypothesis that the combination of AC and NO to treat DCU is possible. In this study we considered gels of AC and NO, and evaluated the effects of the gel on DCU healing. Based on our study, it was found that the combined effect of asiaticoside and NO could accelerate the healing rate of DCU wounds. The asiaticoside NO gel can inhibit the growth of bacteria in the wound surface, alleviate the inflammatory reaction of wound, and increase the expression of VEGF, iNOS, eNOS and CD34. Our research shows that asiaticoside NO gel may promote DCU wound healing by regulating Wnt/ß-Catenin signaling pathway. It will provide new targets and strategies for the diagnosis and treatment of DCU.

[Effects of rutaecarpine on inflammatory cytokines in insulin resistant primary skeletal muscle cells].

It is now well established that inflammation plays an important role in the development of numerous chronic metabolic diseases including insulin resistance (IR) and type 2 diabetes (T2DM). Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Our pre- vious study has shown that rutaecarpine (Rut) can benefit blood lipid profile, mitigate inflammation, and improve kidney, liver, pan- creas pathology status of T2DM rats. However, the effects of Rut on inflammatory cytokines in the development of IR-skeletal muscle cells have not been studied. Thus, our objective was to investigate effects of Rut on inflammatory cytokines interleukiri (IL)-1, IL-6 and tumor necrosis factor (TNF)-α in insulin resistant primary skeletal muscle cells (IR-PSMC). Primary cultures of skeletal muscle cells were prepared from 5 neonate SD rats, and the primary rat skeletal muscle cells were identified by cell morphology, effect of ru- taecarpine on cell proliferation by MTT assay. IR-PSMC cells were induced by palmitic acid (PA), the glucose concentration was measured by glucose oxidase and peroxidase (GOD-POD) method. The effects of Rut on inflammatory cytokines IL-1, IL-6 and TNF-α in IR-PSMC cells were tested by enzyme-linked immunosorbent assay (ELISA) kit. The results show that the primary skeletal muscle cells from neonatal rat cultured for 2-4 days, parallel alignment regularly, and cultured for 7 days, cells fused and myotube formed. It was shown that Rut in concentration 0-180. 0 µmol x L(-1) possessed no cytotoxic effect towards cultured primary skeletal muscle cells. However, after 24 h exposure to 0.6 mmol x L(-1) PA, primary skeletal muscle cells were able to induce a state of insulin resistance. The results obtained indicated significant decrease (P < 0.05 to P < 0.001) IL-1, IL-6 and TNF-α production by cultured IR-PSMC cells when incubating 24 hours with Rut, beginning from 20 to 180.0 µmol x L(-1). IL-1, IL-6 and TNF-α in the Rut treated groups were dose-dependently decreased compared with that in the IR-PSMC control group. Our results demonstrated that the Rut promoted glucose consumption and improved insulin resistance possibly through suppression of inflammatory cytokines in the IR-PSMC cells.

[Probe excavations about using gene chip to identify original plants in Chinese pharmacopoeia based on NCBI sequence database].

OBJECTIVE: Based on the DNA fragments of medicinal plants of NCBJ database, the DNA Probe,which can be used to identify original plants in the Chinese Pharmacopoeia (2010 edition), was got. METHODS: First of all, get the Latin name of the original plants by collating the Chinese Pharmacopoeia. Next,download the medicinal plants' DNA fragments from the NCBI database, including ITS, matK, rbcL, psbK-psbI and trnH-psbA, then design probe by using Array Designer 4. 2. Finally, analyze each probe's versatility in the same kind of original plant and conservatism in different kinds of original plants by using Matlab, then determine the specificity of the probe. RESULTS: Regarding the Latin name of 586 original plants in the Chinese Pharmacopoeia (2010 edition) and the above five gene fragments as retrieval condition, 7 613 sequences were downloaded from NCBI, then 315 436 probes were got in total by analyzing. What's more, after analyzing versatility and conservatism of the probes,13 814 specific probes were got. Furthermore,in theory, 376 kinds of original plants could be detected. Because there existed the lack of related gene fragments in the NCBI database,or the sequences were short of specificity,210 species of original plants which were involved in the Chinese Pharmacopoeia didn't receive the corresponding probe. CONCLUSION: The results of the study can provide the further development of medicinal plants' identification chip with vital information support,and the excavation methods of probe can be widely used. Furthermore,the results of the study indicate the original plants which need sequencing importantly in the future.

[Effects of four kinds of Chinese medicine monomer on growth of PANC-1 xenograft tumor and studying of molecular mechanism].

OBJECTIVE: The antitumor effects of icarisid II, timosaponin A-III, neferine and salidroside were studied in PANC-1 xenograft tumor. METHOD: To establish of the nude mice xenograft tumor model, PANC-1 cells were injected. When the tumor major diameter was reached 3-5 mm, the treatment was initiated. The mice were randomized into vehicle control and treatment groups of six animals per each. Chinese medicine monomer was injected intraperitoneally every day. In 23th day, mice were killed once a day, tumor tissue were isolated and weighed and divided into two parts. One part was fixed with formaldehyde for tissue section and immunohistochemistry, the another of tissue was frozen in liquid nitrogen then in - 80 degrees C refrigerator for gene and protein expression analysis. RESULT: In PANC-1 tumor xenograft experiment, compared with model group, timosaponin A-III (1.0 mg x kg (-1)) exerted significant inhibitory effects on tumor growth. Timosaponin A-III suppressed mRNA expressions of VEGF (P < 0.05), reduced protein expressions of VEGF (P < 0.05), activated Caspase-3 protein. Icarisid II, neferine and salidroside had not an excelled antitumor effect. CONCLUSION: Timosaponin A-III exerted an excelled antitumor effect. The antitumor mechanisms include anti-angiogenesis, apoptosis promotion.

[Diabetes mellitus ulcers treatment with Bletilla striata polysaccharide].

The aim of this study was to evaluate the efficacy of Bletilla striata polysaccharide on diabetes mellitus ulcers. Diabetes mellitus animal model was established by single ip injection of streptozotocin (STZ, 50 mg x kg(-1)) with the criteria of blood glucose > or = 16.7 mmol x L(-1) after 72 h. 4 weeks after STZ injection, each animal received two full thickness incisional wounds (1.8 cm in diameter). The wounds then were divided into B. striata polysaccharide group and PBS group. Wound closure rate, fibroblast (FB) infiltration, hydroxyproline (OHP) content and myeloperoxidase (MPO) levels were examined on day 3, 7, 14, 21 post wound. The treatment of B. striata polysaccharide significantly facilitated diabetes mellitus ulcers healing compared to PBS group. Histological analysis showed that B. striata polysaccharide markedly increased inflammatory cell infiltration in wound area. The herb also strongly evaluation of FB, OHP demonstrated a significantly increased in B. striata polysaccharide group. B. striata polysaccharide group promoted wound closure by means of enhanced inflammatory cell infiltration and re-epithelialization, and the promotion of FB and OHP levels.

[Study on effect of total saponins from Semen Nigellae on inflammatory mediators and ERK/MAPK pathway in stimulated macrophage].

OBJECTIVE: To study the anti-inflammatory mechanism of total saponins from Semen Nigellae (TSSN). METHOD: IFN-gamma plus LPS stimulated RAW 264. 7 macrophage has been used as inflammatory experimental model. Griess reaction for nitric oxide production, FRAP assay for total antioxidant capacity, RT-PCR for mRNA expression and Western blot for protein expression examination were performed. RESULT: TSSN inhibited NO production in a dose-dependent manner. The gene and protein expression of iNOS were also suppressed by the herb extract. TSSN treatment significantly attenuated mRNA of inflammatory mediators such as COX-2, IL-1beta, IL-6 while increased PPAR-gamma gene and protein expression. Furthermore, phosphorylation of ERK (p-ERK) was markedly inhibited by TSSN. CONCLUSION: TSSN suppressed pro-inflammatory mediators such as COX-2, IL-1beta, IL-6 and increased anti-inflammatory mediator PPAR-gamma expression. Meanwhile, TSSN inhibited over production of NO and iNOS expression through ERK/MAPK pathway.