Ethnobotanical Survey on Bitter Tea in Taiwan.

Ethnopharmacological evidence: In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea plant, Camellia sinensis (L.) Kuntze. Bitter tea (kǔ-chá), a series of herbal teas prepared in response to common diseases in Taiwan, is often made from local Taiwanese plants. However, the raw materials and formulations have been kept secret and verbally passed down by store owners across generations without a fixed recipe, and the constituent plant materials have not been disclosed. Aim of the study: The aim was to determine the herbal composition of bitter tea sold in Taiwan, which can facilitate further studies on pharmacological applications and conserve cultural resources. Materials and methods: Interviews were conducted through a semi-structured questionnaire. The surveyed respondents were traditional sellers of traditional herbal tea. The relevant literature was collated for a systematic analysis of the composition, characteristics, and traditional and modern applications of the plant materials used in bitter tea. We also conducted an association analysis of the composition of Taiwanese bitter tea with green herb tea (qing-cao-cha tea), another commonly consumed herbal tea in Taiwan, as well as herbal teas in neighboring areas outside Taiwan. Results: After visiting a total of 59 stores, we identified 32 bitter tea formulations and 73 plant materials. Asteraceae was the most commonly used family, and most stores used whole plants. According to a network analysis of nine plant materials used in high frequency as drug pairs, Tithonia diversifolia and Ajuga nipponensis were found to be the core plant materials used in Taiwanese bitter tea. Conclusion: Plant materials used in Taiwanese bitter tea were distinct, with multiple therapeutic functions. Further research is required to clarify their efficacy and mechanisms.

An Ethnobotanical Study on Qing-Cao-Chá Tea in Taiwan.

Herbal tea, a beverage prepared from a variety of plant materials excluding the leaves of the tea plant Camellia sinensis (L.) Kuntze of the family Theaceae, for a long time, has been consumed by most Chinese people for preventive and/or therapeutic health care. Usually, it is brewed or prepared as a decoction of local plants in water. The qing-cao-chá tea, a commercial herbal tea, is the most common among many differently formulated herbal teas in Taiwan. For hundreds of years, qing-cao-chá tea has played an important role in the prevention and treatment of diseases associated with the environmental conditions in Taiwan. However, research studies in this field have been insufficient. The raw material formulas of qing-cao-chá tea have always been passed down from "masters" to "apprentices." Hence, there is no systematic collation or record, and, therefore, there is a need to assess and confirm the composition, safety, and effectiveness of the raw materials. This study aimed to document the uses of Taiwan's qing-cao-chá tea through a semi-structured interview survey and investigate the background of traditional practitioners, tea compositions, and plant origins and uses. This will improve our understanding of the knowledge inherited by the practitioners and the theoretical basis of the medicinal uses of these teas. In our field investigation, we visited 86 shops and assessed 71 raw ingredients of qing-cao-chá tea. A semi-structured questionnaire was used to conduct the interviews. During the interviews, in addition to written records, audio and video recordings were made, and photographs were taken with the permission of the interviewees. The qing-cao-chá raw materials have long been used as herbal teas, although more research should clarify their efficacy and safety. Traditional sellers of qing-cao-chá tea were mainly males, and most shops have been in operation for more than 71 years. Some of the raw materials were derived from multiple sources, including different plants, and were often mixed without any safety concerns. To our knowledge, this is the first systematic ethnobotanical study on qing-cao-chá tea that assesses and confirms its herbal ingredients. Our study represents a reference for herbal teas in Taiwan that can be used by the public and regulatory agencies.

Gallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet-and Streptozotocin-Induced NAFLD and Diabetes through Improvement of ß-oxidation and Ketogenesis.

Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of ß-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.

Effects of processing adjuvants on traditional Chinese herbs.

Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs). Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs.

Major achievements of evidence-based traditional Chinese medicine in treating major diseases.

A long history of use and extensive documentation of the clinical practices of traditional Chinese medicine resulted in a considerable number of classical preparations, which are still widely used. This heritage of our ancestors provides a unique resource for drug discovery. Already, a number of important drugs have been developed from traditional medicines, which in fact form the core of Western pharmacotherapy. Therefore, this article discusses the differences in drug development between traditional medicine and Western medicine. Moreover, the article uses the discovery of artemisinin as an example that illustrates the "bedside-bench-bedside" approach to drug discovery to explain that the middle way for drug development is to take advantage of the best features of these two distinct systems and compensate for certain weaknesses in each. This article also summarizes evidence-based traditional medicines and discusses quality control and quality assessment, the crucial steps in botanical drug development. Herbgenomics may provide effective tools to clarify the molecular mechanism of traditional medicines in the botanical drug development. The totality-of-the-evidence approach used by the U.S. Food and Drug Administration for botanical products provides the directions on how to perform quality control from the field throughout the entire production process.

Improving the Concentrations of the Active Components in the Herbal Tea Ingredient, Uraria crinita: The Effect of Post-harvest Oven-drying Processing.

Uraria crinita is widely used as a popular folk drink; however, little is known about how the post-harvest operations affect the chemical composition and bioactivity of UC. We assessed three drying methods (Oven-drying, Air-drying, Sun-drying), as well as the Oven-drying temperature using metabolomics approaches and bioactivity assays. The samples processed at 40 degree show a greater effect on the levels of estrogen receptor-alpha activity and nuclear factor erythroid 2-related factor 2 activity, anti-oxidative activity, and cyclooxygenase-2 inhibition compared with the other samples. A multivariate analysis showed a clear separation between the 40 degree Oven-dried samples and the other samples, which is consistent with the results of bioactivity assay. These results are ascribed to at least two-fold increase in the concentrations of flavonoids, spatholosineside A and triterpenoids in the oven-dried samples compared with the other groups. The proposed Oven-drying method at 40 degree results in an improved quality of UC.

Chinese herbal medicines promote hippocampal neuroproliferation, reduce stress hormone levels, inhibit apoptosis, and improve behavior in chronically stressed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: An efficacious antidepressant without unwanted side effects is need urgently at present. This study aimed to investigate whether treatment with four Chinese herbal medicines (CHMs), namely Radix Astragali, Saposhnikovia divaricate (SD), Eucommia ulmoides Oliv. bark (EU), and Corydalis yanhusuo W. T. Wang (C. yanhusuo), could reverse the effects of chronic mild stress (CMS) in a depression-like mouse model and the potential mechanism(s) of their action. MATERIALS AND METHODS: In vitro study, the proliferation of NSCs was assessed using the MTS assay. In vivo study, chronic mild stress (CMS) was used in mice for 14 days to establish a depression-like mouse model. Plasma corticosterone levels were assessed by UPLC coupled to a triple-quadrupole mass spectrometer. The forced swim test (FST) was used to assess the effects of the four CHMs on depression. BrdU incorporation and TUNEL staining were used to assay hippocampal precursor cell proliferation rate and apoptosis. RESULTS: The CHMs included Radix Astragali, EU, C. yanhusuo, and SD were shown to promote neuroproliferation in vitro. In vivo study, oral administration of these four CHMs for 14 days reversed the elevated plasma corticosterone levels, body weight loss, decrease in proliferation of hippocampal precursor cells; they also inhibited hippocampal cell apoptosis, and exhibited an antidepressant-like effect in a depression-like mouse model induced by CMS. CONCLUSIONS: Our study indicates that each of these CHMs has the potential to ameliorate depression. The possible mechanisms of action include modulation of the HPA axis, reduction in stress hormone levels, inhibition of apoptosis, and promotion of hippocampal neuronal plasticity and neurogenesis.

Gallic acid ameliorated impaired glucose and lipid homeostasis in high fat diet-induced NAFLD mice.

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more "holistic view" approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.

Antioxidant, Analgesic, Anti-Inflammatory, and Hepatoprotective Effects of the Ethanol Extract of Mahonia oiwakensis Stem.

The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOS(EtOH)). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOS(EtOH) was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOS(EtOH) exhibited antioxidative activity using the DPPH assay (IC(50), 0.743 mg/mL). The DPPH radical scavenging activity of MOS(EtOH) was five times higher that that of vitamin C. MOS(EtOH) was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOS(EtOH) (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl(4)-treated group. Histological evaluation showed that MOS(EtOH) reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOS(EtOH) were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOS(EtOH) has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOS(EtOH) for relieving pain and inflammation in folk medicine.

Three Chinese herbal medicines promote neuroproliferation in vitro, and reverse the effects of chronic mild stress on behavior, the HPA axis, and proliferation of hippocampal precursor cell in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: The present study investigated whether Chinese herbal medicines (CHMs) could reverse the effects of chronic mild stress (CMS) in a depression-like mouse model. MATERIALS AND METHODS: The effects of three Chinese herbals, Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri on promoting neuroproliferation were evaluated in vitro first and followed by in vivo study of mice which were received by an experimental setting of CMS for 14 days. The effects of the three CHMs on depression were evaluated using a behavioral test, named a forced swimming test (FST). The possible anti-depressive mechanisms of these three CHMs, including the modulation of HPA axis and promoting the hippocampal precursor cell proliferation, were evaluated by measuring plasma corticosterone levels and BrdU incorporation. RESULTS: The in vitro results of MTS assay showed that Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri could promote the proliferation of neural stem cells (NSCs) in a concentration-dependent manner. The oral administration of these three CHMs for 14 days reversed not only the elevation of plasma corticosterone levels and body weight loss, but also the decreasing of hippocampal precursor cell proliferation and abnormal behavior in the CMS induced depression-like mouse model. CONCLUSION: These results indicated that Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri have the potential to ameliorate depression. The possible mechanisms were the inhibition of HPA axis hyperactivity and the increasing of hippocampal precursor cell proliferation. These findings supported the multicomponent and multitargeted approach of Chinese herbal medicine.

Evaluation of chinese-herbal-medicine-induced herb-drug interactions: focusing on organic anion transporter 1.

The consumption of Chinese herbal medicines (CHMs) is increasing exponentially. Many patients utilize CHMs concomitantly with prescription drugs in great frequency. Herb-drug interaction has hence become an important focus of study. Transporter-mediated herb-drug interactions have the potential to seriously influence drug efficacy and toxicity. Since organic anion transporter 1 (OAT1) is crucial in renal active secretion and drug-drug interactions, the possibility of modulation of OAT1-mediated drug transport should be seriously concerned. Sixty-three clinically used CHMs were evaluated in the study. An hOAT1-overexpressing cell line was used for the in vitro CHMs screening, and the effective candidates were administered to Wistar rats to access renal hemodynamics. The regulation of OAT1 mRNA expression was also examined for further evidence of CHMs affecting OAT1-mediated transport. Among all the 63 CHMs, formulae Gui Zhi Fu Ling Wan (GZ) and Chia Wei Hsiao Yao San (CW) exhibited significant inhibitions on hOAT1-mediated [(3)H]-PAH uptake in vitro and PAH clearance and net secretion in vivo. Moreover, GZ showed concentration-dependent manners both in vitro and in vivo, and the decrease of rOAT1 mRNA expression indicated that GZ not only inhibited function of OAT1 but also suppressed expression of OAT1.

Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo.

The purpose of this study is to evaluate the effects of Chinese herbal medicines on the enzymatic activity of CYP3A4 and the possible metabolism-based herb-drug interactions in human liver microsomes and in rats. Fifty single-herbal preparations were screened for the activity of CYP3A4 using human liver microsomes for an in vitro probe reaction study. The enzymatic activity of CYP3A4 was estimated by determing the 6ß-hydroxytestosterone metabolized from testosterone performed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Huang Qin (Scutellaria baicalensis Geprgi), Mu Dan Pi (Paeonia suffruticosa Andr.), Ji Shiee Terng (Spatholobus suberectus Dunn.) and Huang Qi (Astragalus membranaceus [Fisch] Bge) have been demonstrated to have remarkable inhibiting effects on the metabolism of CYP3A4, whereas Xi Yi Hua (Magnolia biondii Pamp.) exhibited a moderate inhibition. These five single herbs were further investigated in an animal study using midazolam. Mu Dan Pi, Ji Shiee Terng and Huang Qi were observed to have greatly increased in the C(max) and AUC of midazolam. This study provides evidence of possible herb-drug interactions involved with certain single herbs.

In vitro and in vivo evaluation of the metabolism and pharmacokinetics of sebacoyl dinalbuphine.

A diester prodrug of nalbuphine, sebacoyl dinalbuphine (SDN), and its long-acting formulation are currently being developed to prolong the duration of nalbuphine. A comparative in vitro hydrolysis study was conducted for SDN in rat, rabbit, dog, and human blood. Both SDN and nalbuphine in blood or plasma were measured by high-performance liquid chromatography. The hydrolysis rates of SDN in blood were ranked as follows: rat > rabbit > human > dog. The rapid formation of nalbuphine in the blood accounted for almost 100% of the prodrug, which supported the contention that nalbuphine is the major metabolite after SDN hydrolysis. The hydrolysis profiles of SDN were similar both in plasma and in red blood cells when compared in the blood. In vitro release results of SDN long-acting formulation showed that the rate-limited step of SDN hydrolysis to nalbuphine in blood is the penetration of SDN from oil into the blood. After intravenous administration of SDN in sesame oil into rats, nalbuphine quickly appeared in plasma and, thereafter, exhibited monoexponential decay. Pharmaceutical dosage forms affecting the drug disposition kinetics were demonstrated after intravenous administration. The AUC of nalbuphine was significantly higher and clearance was significantly lower, without changes in the t(1/2) of nalbuphine after intravenous dosing of SDN in sesame oil when compared with that of intravenous dosing with nalbuphine HCl in rats. Overall, these results suggest that SDN fulfilled the original pro-soft drug design in which the prodrug can rapidly metabolize to nalbuphine, and no other unexpected compounds were apparent in the blood.