Tea and tea drinking: China's outstanding contributions to the mankind.

BACKGROUND: Tea trees originated in southwest China 60 million or 70 million years ago. Written records show that Chinese ancestors had begun drinking tea over 3000 years ago. Nowadays, with the aging of populations worldwide and more people suffering from non-communicable diseases or poor health, tea beverages have become an inexpensive and fine complementary and alternative medicine (CAM) therapy. At present, there are 3 billion people who like to drink tea in the world, but few of them actually understand tea, especially on its development process and the spiritual and cultural connotations. METHODS: We searched PubMed, Google Scholar, Web of Science, CNKI, and other relevant platforms with the key word "tea", and reviewed and analyzed tea-related literatures and pictures in the past 40 years about tea's history, culture, customs, experimental studies, and markets. RESULTS: China is the hometown of tea, tea trees, tea drinking, and tea culture. China has the oldest wild and planted tea trees in the world, fossil of a tea leaf from 35,400,000 years ago, and abundant tea-related literatures and art works. Moreover, tea may be the first Chinese herbal medicine (CHM) used by Chinese people in ancient times. Tea drinking has many benefits to our physical health via its antioxidant, anti-inflammatory, immuno-regulatory, anticancer, cardiovascular-protective, anti-diabetic, and anti-obesity activities. At the moment, COVID-19 is wreaking havoc across the globe and causing severe damages to people's health and lives. Tea has anti-COVID-19 functions via the enhancement of the innate immune response and inhibition of viral growth. Besides, drinking tea can allow people to acquire a peaceful, relaxed, refreshed and cheerful enjoyment, and even longevity. According to the meridian theory of traditional Chinese medicine, different kinds of tea can activate different meridian systems in the human body. At present, black tea (fermented tea) and green tea (non-fermented tea) are the most popular in the world. Black tea accounts for over 90% of all teas sold in western countries. The world's top-grade black teas include Qi Men black in China, Darjeeling and Assam black tea in India, and Uva black tea in Sri Lanka. However, all top ten famous green teas in the world are produced in China, and Xi Hu Long Jing tea is the most famous among all green teas. More than 700 different kinds of components and 27 mineral elements can be found in tea. Tea polyphenols and theaflavin/thearubigins are considered to be the major bioactive components of black tea and green tea, respectively. Overly strong or overheated tea liquid should be avoided when drinking tea. CONCLUSIONS: Today, CAM provides an array of treatment modalities for the health promotion in both developed and developing countries all over the world. Tea drinking, a simple herb-based CAM therapy, has become a popular man-made non-alcoholic beverage widely consumed worldwide, and it can improve the growth of economy as well. Tea can improve our physical and mental health and promote the harmonious development of society through its chemical and cultural elements.

Evaluation of Beneficial and Adverse Effects of a Diet Supplemented with Schisandrae Fructus Seed Ethanol Extract on Lipid and Glucose Metabolism in Normal and Hypercholesterolemic/Hyperglycemic Mice.

Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baillon, has been used for the treatment of liver injury and metabolism-related disorders in China. The objective of this study was to investigate the effects of supplementation with ethanol extract of SF seed (EtSF-S) on serum/hepatic lipid and glucose levels as well as fecal total cholesterol (TC) contents in mice fed a normal diet (ND) or high-fat/fructose diet (HFFD) containing 15% lard oil and 15% fructose. Female ICR mice (18-20 g in body weight) were fed with ND or HFFD for 3 months, and then EtSF-S was added to both chow diets at increasing concentrations of 1, 5, and 10% (w/w). Thirty days later, serum and hepatic lipids, including TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose, were measured. Dietary supplementation with EtSF-S reduced hepatic TC (36 and 18%) and TG levels (38 and 28%) and increased serum HDL/LDL ratio (16 and 26%) in both ND- and HFFD-fed mice, respectively. Moreover, supplementation with EtSF-S elevated serum HDL (31%) in HFFD-fed mice and reduced serum LDL (27%) in ND-fed mice. EtSF-S treatment reduced fat mass (40%) in ND-fed mice and increased fecal TC contents (33%) in HFFD-fed mice. EtSF-S supplementation decreased hepatic glucose contents (29%) in both ND- and HFFD-fed mice. However, diet supplemented with EtSF-S elevated serum TG levels (up to 123%) and hepatic size (28%), but more importantly, suppressed the body weight gain (approximately 130%) in mice fed with HFFD. These findings suggested that dietary supplementation with EtSF-S as natural herbal function food may be a useful strategy for the treatment of patients with fatty liver disease or overweight without a high intake of sugar and fat.

Dingchuan tang essential oil inhibits the production of inflammatory mediators via suppressing the IRAK/NF-κB, IRAK/AP-1, and TBK1/IRF3 pathways in lipopolysaccharide-stimulated RAW264.7 cells.

BACKGROUND: Dingchuan tang (asthma-relieving decoction), a formula of nine herbs, has been used for treating respiratory inflammatory diseases for >400 years in the People's Republic of China. However, the mechanisms underlying the anti-inflammatory action of dingchuan tang is not fully understood. This study aims to investigate the effects of Dingchuan tang essential oil (DCEO) on inflammatory mediators and the underlying mechanism of action. MATERIALS AND METHODS: DCEO was extracted by steam distillation. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were used as the cell model. Production of nitric oxide (NO) was determined by the Griess test. Protein secretion and mRNA levels of inflammatory mediators were measured by the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Protein levels were examined by Western blot. Nuclear localization of nuclear factor-kappa B (NF-κB) was detected using immunofluorescence analyses. RESULTS: DCEO significantly reduced LPS-triggered production of NO and prostaglandin E2 (PGE2) and decreased protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). LPS induced upregulation of protein and mRNA levels of cytokines (interleukin-1ß [IL-1ß], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α]), and chemokines (monocyte chemoattractant protein-1 [MCP-1], chemokine [C-C motif] ligand 5 [CCL-5], and macrophage inflammatory protein [MIP]-1α) were suppressed by DCEO treatment. Phosphorylation and nuclear protein levels of transcription factors (activator protein-1 [AP-1], NF-κB, interferon regulatory factor 3 [IRF3]) were decreased by DCEO. Protein levels of phosphorylated IκB-α, IκB kinase α/ß (IKKα/ß), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), TGF ß-activated kinase 1 (TAK1), TANK-binding kinase 1 (TBK1), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) were lowered by DCEO. Moreover, degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 induced by LPS was inhibited by DCEO treatment. CONCLUSION: Suppression of the interleukin-1 receptor-associated kinase (IRAK)/NF-κB, IRAK/AP-1 and TBK1/IRF3 pathways was associated with the inhibitory effects of DCEO on inflammatory mediators in LPS-stimulated RAW264.7 macrophages. This study provides a pharmacological justification for the use of dingchuan tang in managing inflammatory disorders.

Biochemical mechanism underlying hypertriglyceridemia and hepatic steatosis/hepatomegaly induced by acute schisandrin B treatment in mice.

BACKGROUND: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. METHODS: Male ICR mice were given a single oral dose of Sch B (0.25-2 g/kg). Sch B-induced changes in serum levels of biomarkers, such as TG, total cholesterol (TC), apolipoprotein B48 (ApoB 48), very-low-density lipoprotein (VLDL), non-esterified fatty acid (NEFA) and hepatic growth factor (HGF), as well as hepatic lipids and mass, epididymal adipose tissue (EAT) and adipocyte size, and histological changes of the liver and EAT were examined over a period of 12-120 h after Sch B treatment. RESULTS: Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h, respectively, after Sch B administration. Sch B treatment elevated serum ApoB 48 level (up to 12%), a marker of exogenous TG, but not VLDL, as compared with the vehicle treatment. Treatment with Sch B caused a time-/dose-dependent reduction in EAT index (up to 39%) and adipocyte size (up to 67%) and elevation in serum NEFA level (up to 55%). Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs. the vehicle control) and lipid positive staining area (up to 17.5 × 103 µm2) in liver tissue. Hepatic index and serum HGF levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively. In addition, ultrastructural changes, such as increase in size and disruption of cristae, in hepatic mitochondria were observed in Sch B-treated mice. CONCLUSION: Our findings suggest that exogenous sources of TG and the breakdown of fat storage in the body contribute to Sch B-induced hypertriglyceridemia and hepatic steatosis in mice. Hepatomegaly (a probable hepatotoxic action) caused by Sch B may result from the fat accumulation and mitochondrial damage in liver tissue.

Jiang Tang Xiao Ke Granule, a Classic Chinese Herbal Formula, Improves the Effect of Metformin on Lipid and Glucose Metabolism in Diabetic Mice.

In the present study, the hypoglycemic, hypolipidemic, and antioxidative effects of metformin (MET) combined with Jiang Tang Xiao Ke (JTXK) granule derived from the "Di Huang Tang" were evaluated in mice with type 2 diabetes mellitus (DM) induced by high-fat diet/streptozotocin. DM mice were orally treated with MET (0.19 g/kg) either alone or combined with different doses (1.75, 3.5, or 7 g/kg) of JTXK for 4 weeks. Results showed that the serum and hepatic glucose, lipids, and oxidative stress levels were elevated in DM mice, when compared with the normal mice. MET treatment decreased FBG and serum glucagon levels of DM mice. Combination treatment with MET and JTXK 3.5 g/kg increased the hypoglycemia and insulin sensitivity at 4 weeks when compared with the DM mice treated with MET alone. However, neither MET nor MET/JTXK treatment could completely reverse the hyperglycemia in DM mice. JTXK enhanced the serum triglyceride (TG) and hepatic lipid-lowering effect of MET in a dose-dependent manner in DM mice. JTXK 1.75 and 3.5 g/kg improved the hepatoprotective effect of MET in DM mice. Synergistic effect of combination treatment with MET and JTXK on antioxidant stress was also found in DM mice compared with MET alone.

A comparative study between Wuweizi seed and its post-ethanol extraction residue in normal and hypercholesterolemic mice.

BACKGROUND: At the present, a shift from drug therapy, especially herbal therapy, to dietary supplementation is a trend in the management of dyslipidemia and related diseases. Therefore, the optimal utilization of herbal resource is important for a sustainable development of herbal medicine. Here, we compared the effects of dietary supplementation with Chinese medicine Schisandrae Chinensis Fructus seed (FSC-S) and the post-ethanol extraction residue of FSC-S (FSC-SpEt) on normal diet-fed (normal) and experimental hypercholesterolemic (HCL) mice. METHODS: Male ICR mice (n = 10 in each group), weighing 17-21 g, were fed with normal diet (ND) or high cholesterol/bile salt (1/0.3 %, w/w) diet (HCBD) with or without supplemented with FSC-S, FSC-SpEt), or lipid-lowering agent fenofibrate (FF). Ten days later, serum/hepatic lipid and glucose (GLU) levels, body weight, organ/epididymal fat masses, and food/water intake were measured. Lipid level measurements included those of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), HDL/LDL ratio, LDL/HDL ratio, and non-HDL (N-HDL). RESULTS: Supplementation with FSC-S and FSC-SpEt increased serum TC (by 64 and 25 %, respectively) and LDL (by 60 and 27 %, respectively) in normal mice. FSC-S supplementation elevated serum TC, TG, HDL, LDL, and LDL/HDL ratio (up to 64, 118, 77, 197, and 51 %, respectively) in HCL mice. FSC-SpEt supplementation reduced serum TG (by 15 %) and LDL/HDL ratio (by 18 %), as well as increased serum HDL (by 22 %) and HDL/LDL ratio (by 21 %) in HCBD-fed mice. FSC-S decreased hepatic TC (by 19 %) contents and increased hepatic TG contents by 14 % in normal mice. FSC-S reduced hepatic GLU level in both normal and HCL mice by 24 and 22 %, respectively. Hepatic TC and TG contents were lowered in FSC-SpEt-supplemented normal mice by 16 and 20 %, respectively. The body/fatty masse and food intake were lowered, but the feed efficiency index (FEI), weight gain per unit of food ingested, was increased in FSC-S-supplemented normal and HCL mice. FF supplements reduced serum/hepatic lipids, hepatic GLU contents, and epididymal fat mass, but it induced hepatomegaly and high serum alanine aminotransferase (ALT) activity in normal and/or HCL mice. CONCLUSION: The ensemble of results indicated that while FSC-SpEt supplementation is beneficial for the treatment of hyperlipidemia/fatty liver, FSC-S is potentially useful for the management of overweight/obesity.

Schisandrin B inhibits cell growth and induces cellular apoptosis and autophagy in mouse hepatocytes and macrophages: implications for its hepatotoxicity.

A number of drugs and herbal compounds have been documented to cause hepatoxicity. Schisandrin B (Sch B) is an active dibenzocyclooctadiene isolated from Schisandrae fructus, with a wide array of pharmacological activities. However, the potential hepatotoxicity of Sch B is a major safety concern, and the underlying mechanism for Sch B-induced liver toxic effects is not fully elucidated. In the present study, we aimed to investigate the liver toxic effects and the molecular mechanisms of Sch B in mouse liver and macrophage cells. The results have shown that Sch B exhibits potent grow inhibitory, proapoptotic, and proautophagic effects in AML-12 and RAW 264.7 cells. Sch B markedly arrested cells in G1 phase in both cell lines, accompanied by the down-regulation of cyclin dependent kinase 2 (CDK2) and cyclin D1 and up-regulation of p27 Kip1 and checkpoint kinase 1. Furthermore, Sch B markedly increased the apoptosis of AML-12 and RAW 264.7 cells with a decrease in the expression of B-cell lymphoma-extra-large and (Bcl-xl) B-cell lymphoma 2 (Bcl-2), but an increase in the expression of B-cell lymphoma 2-associated X protein (Bax). Sch B promoted the cleavage of caspase 3 and poly-adenosine diphosphate-ribose polymerase (PARP) in both cell lines. Additionally, Sch B significantly induced autophagy of AML-12 and RAW 264.7 cells. Sch B inhibited the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, as indicated by their altered phosphorylation, contributing to the proautophagic effect of Sch B. Taken together, our findings show that the inducing effects of Sch B on cell cycle arrest, apoptosis, and autophagy may contribute to its liver toxic effects, which might provide a clue for the investigation of the molecular toxic targets and underlying mechanisms for Sch B-induced hepatotoxicity in herbal consumers. More studies are warranted to fully delineate the underlying mechanisms, efficacy, and safety of Sch B for clinical use.

Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers.

Schisandrin B (SchB) is one of the most abundant bioactive dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis. Here, we investigated the potential therapeutic effects of SchB on non-alcoholic fatty-liver disease (NAFLD). In lipidomic study, ingenuity pathway analysis highlighted palmitate biosynthesis metabolic pathway in the liver samples of SchB-treated high-fat-diet-fed mice. Further experiments showed that the SchB treatment reduced expression and activity of fatty acid synthase, expressions of hepatic mature sterol regulatory element binding protein-1 and tumor necrosis factor-α, and hepatic level of palmitic acid which is known to promote progression of steatosis to steatohepatitis. Furthermore, the treatment also reduced hepatic fibrosis, activated nuclear factor-erythroid-2-related factor-2 which is known to attenuate the progression of NASH-related fibrosis. Interestingly, in fasting mice, a single high-dose SchB induced transient lipolysis and increased the expressions of adipose triglyceride lipase and phospho-hormone sensitive lipase. The treatment also increased plasma cholesterol levels and 3-hydroxy-3-methylglutaryl-CoA reductase activity, reduced the hepatic low-density-lipoprotein receptor expression in these mice. Our data not only suggest SchB is a potential therapeutic agent for NAFLD, but also provided important information for a safe consumption of SchB because SchB overdosed under fasting condition will have adverse effects on lipid metabolism.

Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice.

BACKGROUND: Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF), a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb) pulp (AqSF-P) or an SF-related synthetic analog, bicyclol (BY), on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL) mice. METHODS: Male mice obtained from the Institute of Cancer Research (ICR) were fed on a normal diet (ND) or high cholesterol/bile salt (0.5%/0.15%, w/w) diet (HCBD) containing FF (0.03% or 0.1%, w/w) with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w) or BY (0.025%, w/w) for 10 days. Then serum lipid levels and alanine aminotransferase (ALT) activity, as well as hepatic triglyceride (TG), total cholesterol (TC), and glucose levels, were measured. RESULTS: Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79%) in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67%) and in HCBD-fed mice (up to 54%), when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was enhanced (up to 19%) by AqSF-P cosupplementation in both normal and HCL mice. FF supplementation enhanced the excretion of fecal TC (by 75%) in mice fed with HCBD. Fecal TC contents were increased by 14%/9% in the combination therapy with FF and AqSF-P in ND-/HCBD-fed mice. Serum ALT activity was elevated by 45% in HCBD-fed mice. FF caused a significant increase in ALT activity by 198% and 120% in normal and HCL mice, respectively. BY markedly attenuated the ALT activity by 54% in mice fed with ND supplemented with 0.1% FF and by 42% in mice fed with HCBD supplemented with 0.03% FF. CONCLUSION: AqSF-P cosupplementation augmented the hepatic lipid-/glucose-lowering effects of FF. BY ameliorated FF-induced liver injury in normal and HCL mice.

New perspectives on dietary-derived treatments and food safety-antinomy in a new era.

Despite the advances in science and technology and wide use of chemical drugs, dietary intervention (or food therapy) remains useful in preventing or treating many human diseases. A huge body of evidence shows that the dietary pattern or habit is also an important contributing factor to the development of chronic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cancers. In recent years, over-the-counter health foods, nutraceuticals, and plant-derived medicinal products have been gaining popularity all over the world, particularly in developed countries. Unfortunately, owing to the contamination with various harmful substances in foods and the presence of toxic food components, food-borne diseases have also become increasingly problematic. Incidents of food poisonings or tainted food have been increasing worldwide, particularly in China and other developing countries. Therefore, the government should put in a greater effort in enforcing food safety by improving the surveillance mechanism and exerting highest standards of quality control for foods.

Time and dose relationships between schisandrin B- and schisandrae fructus oil-induced hepatotoxicity and the associated elevations in hepatic and serum triglyceride levels in mice.

BACKGROUND: Schisandrin B (Sch B), a dibenzocyclooctadiene compound, is isolated from schisandrae fructus (SF). This study was conducted to compare the time- and dose-response between Sch B- and SF oil (SFO)-induced changes in hepatic and serum parameters in mice. METHODS: Institute of Cancer Research (ICR) mice were given a single oral dose of Sch B (0.125-2 g/kg) or SFO (0.3-5 g/kg). Serum alanine aminotransferase (ALT) activity, hepatic malondialdehyde, and triglyceride (TG) levels were measured at increasing time intervals within 6-120 hours postdosing. RESULTS: Serum ALT activity was elevated by 60%, with maximum effect (E(max)) = 45.77 U/L and affinity (K(D)) = 1.25 g/kg at 48-96 hours following Sch B, but not SFO, treatment. Sch B and SFO treatments increased hepatic malondialdehyde level by 70% (E(max) =2.30 nmol/mg protein and K(D) =0.41 g/kg) and 22% (E(max) = 1.42 nmol/mg protein and K D = 2.56 g/kg) at 72 hours postdosing, respectively. Hepatic index was increased by 16%-60% (E max = 11.01, K(D) = 0.68 g/kg) and 8%-32% (E(max) = 9.88, K D = 4.47 g/kg) at 12-120 hours and 24-120 hours after the administration of Sch B and SFO, respectively. Hepatic TG level was increased by 40%-158% and 35%-85%, respectively, at 12-96 hours and 6-48 hours after Sch B and SFO treatment, respectively. The values of E max and K D for Sch B/SFO-induced increase in hepatic TG were estimated to be 22.94/15.02 µmol/g and 0.78/3.03 g/kg, respectively. Both Sch B and SFO increased serum TG (up to 427% and 123%, respectively), with the values of E(max) = 5.50/4.60 mmol/L and K D = 0.43/2.84 g/kg, respectively. CONCLUSION: The findings indicated that Sch B/SFO-induced increases in serum/hepatic parameters occurred in a time-dependent manner, with the time of onset being serum TG level < hepatic TG level < hepatic index < serum ALT activity. However, the time of recovery of these parameters to normal values varied as follow: serum TG level < hepatic TG level and liver injury < hepatic index. The E max and affinity of Sch B on tissue/enzyme/receptor were larger than those of SFO.

Historical perspective of traditional indigenous medical practices: the current renaissance and conservation of herbal resources.

In recent years, increasing numbers of people have been choosing herbal medicines or products to improve their health conditions, either alone or in combination with others. Herbs are staging a comeback and herbal "renaissance" occurs all over the world. According to the World Health Organization, 75% of the world's populations are using herbs for basic healthcare needs. Since the dawn of mankind, in fact, the use of herbs/plants has offered an effective medicine for the treatment of illnesses. Moreover, many conventional/pharmaceutical drugs are derived directly from both nature and traditional remedies distributed around the world. Up to now, the practice of herbal medicine entails the use of more than 53,000 species, and a number of these are facing the threat of extinction due to overexploitation. This paper aims to provide a review of the history and status quo of Chinese, Indian, and Arabic herbal medicines in terms of their significant contribution to the health promotion in present-day over-populated and aging societies. Attention will be focused on the depletion of plant resources on earth in meeting the increasing demand for herbs.

Supplementation with the extract of schisandrae fructus pulp, seed, or their combination influences the metabolism of lipids and glucose in mice fed with normal and hypercholesterolemic diet.

SCHISANDRAE FRUCTUS (SF), WHICH POSSESSES FIVE TASTES: sweet (fruit skin), sour (pulp), bitter/pungent (seed core), and saltiness (all parts), can produce a wide spectrum of biological activities in the body. Here, we investigated the effects of the ethanolic extract of SF pulp, seed, or their combination (namely, EtSF-P, EtSF-S, or EtSF-P/S, resp.; collectively called EtSF) on the metabolism of lipids and glucose in normal diet- (ND-) and hypercholesterolemic diet- (HCLD-) fed mice. Supplementation with EtSF significantly reduced hepatic triglyceride and cholesterol levels by 18-47% in both ND- and HCLD-fed mice. EtSF supplementation reduced serum triglyceride levels (approximately 29%), whereas EtSF-P and EtSF-S/P elevated serum cholesterol (up to 26 and 44%, resp.) in HCLD-fed mice. Treatment with EtSF decreased hepatic glucose levels (by 9-44%) in both ND- and HCLD-fed mice. Supplementation with EtSF-S or EtSF-S/P (at 1 and 3%) increased biliary or fecal TC contents in HCLD-fed mice. However, supplementation with EtSF-S/P at 9% reduced biliary TC levels in HCLD-fed mice. EtSF-P or EtSF-S/P supplementation reduced serum alanine aminotransferase activity in HCLD-fed mice. The findings suggested that supplementation with EtSF lowered lipid and glucose accumulation in the liver and increased fecal cholesterol contents in mice. Dietary supplementation with EtSF-P or EtSF-S/P attenuated liver damage in HCLD-fed mice.

Dietary pulp from Fructus Schisandra Chinensis supplementation reduces serum/hepatic lipid and hepatic glucose levels in mice fed a normal or high cholesterol/bile salt diet.

BACKGROUND: Recently, it has been found that Fructus Schisandra Chinensis (FSC), a Chinese herbal medicine, and its related compounds have a profound impact on lipid metabolism process. FSC can be divided into two parts, i.e., seed and pulp. The current study aimed to examine the effect of aqueous extracts of FSC pulp (AqFSC-P) on serum/hepatic lipid and glucose levels in mice fed with a normal diet (ND) or a high cholesterol/bile salt diet (HCBD). METHODS: The AqFSC-P used in the present study was fractionated into supernatant (SAqFSC-P) and precipitate (PAqFSC-P) separated by centrifugation. Male ICR mice were fed with ND or HCBD, without or with supplementation of 1%, 3%, or 9% (w/w) SAqFSC-P or PAqFSC-P for 10 days. Biomarkers were determined according to the manufacturer's instruction. RESULTS: Supplementation with SAqFSC-P or PAqFSC-P significantly reduced serum and hepatic triglyceride levels (approximately 40%) in ND- and/or HCBD-fed mice. The supplementation with SAqFSC-P or PAqFSC-P reduced hepatic total cholesterol levels (by 27-46%) in HCBD-fed mice. Supplementation with SAqFSC-P or PAqFSC-P markedly lowered hepatic glucose levels (by 13-30%) in ND- and HCBD-fed mice. SAqFSC-P decreased serum alanine aminotransferase (ALT) activity, but PAqFSC-P increased hepatic protein contents in ND-fed mice. Bicylol, as a positive control, reduced ALT activity. In addition, mice supplemented with FSC-P or bicylol showed a smaller body weight gain and adipose tissue mass as compared to the respective un-supplemented ND- or HCBD-fed mice. CONCLUSION: The results indicate that SAqFSC-P and PAqFSC-P produce hepatic lipid- and glucose-lowering as well as serum TG-lowering effects in hypercholesterolemic mice. FSC pulp may provide a safe alternative for the management of fatty liver and/or lipid disorders in humans.

New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics.

With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM) therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is "experience driven," the search for a therapeutically useful synthetic drug, like "looking for a needle in a haystack," is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development.

Dietary Fructus Schisandrae extracts and fenofibrate regulate the serum/hepatic lipid-profile in normal and hypercholesterolemic mice, with attention to hepatotoxicity.

BACKGROUND: Schisandra, a globally distributed plant, has been widely applied to health care products. Here, we investigated the effects of dietary intake of Fructus Schisandrae chinensis (FSC), both aqueous and ethanolic extracts (AqFSC, EtFSC), on serum/hepatic lipid contents in normal diet (ND)- and high-fat/cholesterol/bile salt diet (HFCBD)-fed mice. METHODS: Male ICR mice were fed with ND or HFCBD, supplemented with 1 and 4% of AqFSC and EtFSC, respectively, or 0.1% fenofibrate, for 13 days. Lipids were determined according to the manufacture's instructions. RESULTS: EtFSC, but not AqFSC, significantly elevated hepatic triglyceride (TG) in mice fed with ND. Feeding mice with HFCBD increased serum total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) levels as well as alanine aminotransferase (ALT) activity. Supplementation with AqFSC, EtFSC or fenofibrate significantly reduced hepatic TC and TG levels. However, AqFSC and EtFSC supplementation increased serum HDL and LDL levels in mice fed with HFCBD. Fenofibrate increased serum HDL and reduced serum LDL contents in hypercholesterolemic mice. EtFSC reduced, but fenofibrate elevated, serum ALT activity in both normal and hypercholesterolemic mice. While fenofibrate reduced serum TC, TG, and HDL levels in mice fed with ND, it increased serum HDL and reduced serum LDL and TC levels in mice fed with HFCBD. Hepatomegaly was found in normal and hypercholesterolemic mice fed with diet supplemented with fenofibrate. CONCLUSIONS: Feeding mice with AqFSC and EtFSC ameliorated the HFCBD-induced hepatic steatosis. In addition, EtFSC may offer protection against hepatic injury in hypercholesterolemic mice.

New perspectives on complementary and alternative medicine: an overview and alternative therapy.

Since 1990, tremendous progress in the medical sciences has precipitated significant improvements in health care. However, with the aging of populations worldwide, more people suffer from noncommunicable disease (NCD), incurable diseases, and/or poor health. The World Health Organization estimated that of the 57 million global deaths in 2008, 36 million were due to NCDs. These pose a considerable challenge to clinicians worldwide, particularly in developed nations. Complementary and alternative medicine (CAM) provides an array of treatment modalities for health promotion. CAM therapy can be divided into two major strategies; namely, herb-based CAM therapy and non-herb based CAM therapy. In the current commentary, we suggest a new understanding of CAM therapy and propose a new classification for CAM therapy as well as alternative therapies. With such information, CAM can be better utilized to benefit to populations worldwide.

Herb-drug interactions and mechanistic and clinical considerations.

Herbal medicines are often used in combination with conventional drugs, and this may give rise to the potential of harmful herb-drug interactions. This paper updates our knowledge on clinical herb-drug interactions with an emphasis of the mechanistic and clinical consideration. In silico, in vitro, animal and human studies are often used to predict and/or identify drug interactions with herbal remedies. To date, a number of clinically important herb-drug interactions have been reported, but many of them are from case reports and limited clinical observations. Common herbal medicines that interact with drugs include St John's wort (Hypericum perforatum), ginkgo (Ginkgo biloba), ginger (Zingiber officinale), ginseng (Panax ginseng), and garlic (Allium sativum). For example, St John's wort significantly reduced the area under the plasma concentration-time curve (AUC) and blood concentrations of cyclosporine, midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline. The common drugs that interact with herbal medicines include warfarin, midazolam, digoxin, amitriptyline, indinavir, cyclosporine, tacrolimus and irinotecan. Herbal medicines may interact with drugs at the intestine, liver, kidneys, and targets of action. Importantly, many of these drugs have very narrow therapeutic indices. Most of them are substrates for cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). The underlying mechanisms for most reported herb-drug interactions are not fully understood, and pharmacokinetic and/or pharmacodynamic mechanisms are implicated in many of these interactions. In particular, enzyme induction and inhibition may play an important role in the occurrence of some herbdrug interactions. Because herb-drug interactions can significantly affect circulating levels of drug and, hence, alter the clinical outcome, the identification of herb-drug interactions has important implications.

New perspectives on chinese herbal medicine (zhong-yao) research and development.

Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.