Polysaccharides derived from natural edible and medicinal sources as agents targeting exercise-induced fatigue: A review.

Exercise-induced fatigue (EF) is a common occurrence during prolonged endurance and excessive exercise and is mainly caused by energy depletion, harmful metabolite accumulation, oxidative stress, and inflammation. EF usually leads to a reduction in initiating or maintaining spontaneous activities and muscle performance and ultimately results in a decrease in the quality of life of people who engage in physical work. Therefore, the interest in investigating EF-targeting agents with minimal side effects and good long-term efficacy has substantially increased. Natural edible and medicinal polysaccharides have shown positive anti-EF effects, but the relevant reviews are rare. This review comprehensively summarizes studies on natural polysaccharides from edible and medicinal sources that can relieve EF and improve physical performance from the past decade, focusing on their sources, monosaccharide compositions, anti-EF effects, and possible molecular mechanisms. Most of these anti-EF polysaccharides are heteropolysaccharides and are mainly composed of glucose, arabinose, galactose, rhamnose, xylose, and mannose. In EF animal models, the polysaccharides exert positive EF-alleviating effects through energy supply, metabolic regulation, antioxidation, anti-inflammation, and gut microbiota remodeling. However, further studies are still needed to clarify the anti-EF effects of these polysaccharides on human beings. In summary, the present review expects to provide scientific data for the future research and development of natural polysaccharide-based anti-EF drugs, dietary supplements, and health-care products for specific fatigue groups.

Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy.

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

Gut mycobiome and metabolic diseases: The known, the unknown, and the future.

Metabolic diseases, such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and obesity, have become a major public health problem worldwide. In recent years, most research on the role of gut microbes in metabolic diseases has focused on bacteria, whereas fungal microbes have been neglected. This review aims to provide a comprehensive overview of gut fungal alterations in T2DM, obesity, and NAFLD, and to discuss the mechanisms associated with disease development. In addition, several novel strategies targeting gut mycobiome and/or their metabolites to improve T2DM, obesity and NAFLD, including fungal probiotics, antifungal drugs, dietary intervention, and fecal microbiota transplantation, are critically discussed. The accumulated evidence suggests that gut mycobiome plays an important role in the occurrence and development of metabolic diseases. The possible mechanisms by which the gut mycobiome affects metabolic diseases include fungal-induced immune responses, fungal-bacterial interactions, and fungal-derived metabolites. Candida albicans, Aspergillus and Meyerozyma may be potential pathogens of metabolic diseases because they can activate the immune system and/or produce harmful metabolites. Moreover, Saccharomyces boulardii, S. cerevisiae, Alternaria, and Cochliobolus fungi may have the potential to improve metabolic diseases. The information may provide an important reference for the development of new therapeutics for metabolic diseases based on gut mycobiome.

Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics.

Fuzi is a famous toxic traditional herbal medicine, which has long been used for the treatment of various diseases in China and many other Asian countries because of its extraordinary pharmacological activities and high toxicity. Different processing methods to attenuate the toxicity of Fuzi are important for its safe clinical use. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with a metabolomics-combined multivariate statistical analysis approach was applied to investigate a series of Aconitum alkaloids and explore potential metabolic markers to understand the differences between raw and processed Fuzi with different steaming time points. Moreover, the selected metabolic markers were visualized by DESI-MSI, and six index alkaloids' contents were determined through HPLC. The results indicated visible differences among raw and processed Fuzi with different steaming times, and 4.0 h is the proper time for toxicity attenuation and efficacy reservation. A total of 42 metabolic markers were identified to discriminate raw Fuzi and those steamed for 4.0 and 8.0 h, which were clearly visualized in DESI-MSI. The transformation from diester-diterpenoid alkaloids to monoester-diterpenoid alkaloids and then to non-esterified diterpene alkaloids through hydrolysis is the major toxicity attenuation process during steaming. DESI-MSI combined with metabolomics provides an efficient method to visualize the changeable rules and screen the metabolic markers of Aconitum alkaloids during steaming. The wide application of this technique could help identify markers and reveal the possible chemical transition mechanism in the "Paozhi" processes of Fuzi. It also provides an efficient and easy way to quality control and ensures the safety of Fuzi and other toxic traditional Chinese medicine.

Gut microbiota-derived metabolites as key actors in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is one of the most risk factors threatening human health. Although genetic and environmental factors contribute to the development of T2DM, gut microbiota has also been found to be involved. Gut microbiota-derived metabolites are a key factor in host-microbe crosstalk, and have been revealed to play a central role in the physiology and physiopathology of T2DM. In this review, we provide a timely and comprehensive summary of the microbial metabolites that are protective or causative for T2DM, including some amino acids-derived metabolites, short-chain fatty acids, trimethylamine N-oxide, and bile acids. The mechanisms by which metabolites affect T2DM have been elaborated. Knowing more about these processes will increase our understanding of the causal relationship between gut microbiota and T2DM. Moreover, some frontier therapies that target gut microbes and their metabolites to improve T2DM, including dietary intervention, fecal microbiota transplantation, probiotics, prebiotics or synbiotics intervention, and drugging microbial metabolism, have been critically discussed. This review may provide novel insights for the development of targeted and personalized treatments for T2DM based on gut microbial metabolites. More high-quality clinical trials are needed to accelerate the clinical translation of gut-targeted therapies for T2DM.

Comparison of medicinal preparations of Ayurveda in India and five traditional medicines in China.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurveda is the main traditional healthcare system in Indian medicine. Tibetan medicine (TM), Mongolian medicine (MM), Buddhist medicine (BM), Dai medicine (DM), and Uyghur medicine (UM) are main traditional medicines practiced in China. These are existing traditional medical systems that still play a role in disease prevention and treatment. AIM OF THE STUDY: To reveal the similarities and differences of traditional medicinal preparations between Ayurveda in India and five traditional medicines in China to deepen medical exchanges and cooperation between the two countries and beyond. METHODS: All preparations were extracted from statutory pharmacopoeias, ministry standards, and prescription textbooks from China and India. The information of each preparation, such as therapeutic uses, medicinal materials, and preparation forms, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 645 Ayurvedic preparations, 458 TM preparations, 164 MM preparations, 616 BM preparations, 227 DM preparations, and 94 UM preparations were identified. Preparations of the six traditional medicines were mostly used for treating digestive, respiratory, and urogenital system diseases. The preparation forms of these six traditional medicines are mainly pills and powders. There are 38 shared-use medicinal materials in Ayurveda and TM preparations, 25 in Ayurveda and MM preparations, 30 in Ayurveda and BM preparations, 39 in Ayurveda and DM preparations, and 31 in Ayurveda and UM preparations. Finally, we selected one important shared-use preparation (Triphala) and 51 medicinal materials to research traditional use and modern pharmacology. CONCLUSIONS: These preparations are used by different prescribers and users of medicinal materials in different medical systems with the similarities and differences. The similarities may reflect the historical exchanges of traditional medicines between the two countries. The differences showed that traditional medicines in China have absorbed some theories, diagnoses, and treatments from Ayurveda but also retained their own ethnic and regional characteristics.

The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence.

Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.

Berberis kansuensis extract alleviates type 2 diabetes in rats by regulating gut microbiota composition.

BACKGROUND: The stem bark of Berberis kansuensis Schneid (BK) is a commonly used Tibetan medicine for the treatment of type 2 diabetes (T2D). However, its therapeutic mechanisms remain unclear. AIM OF THE STUDY: Our aim is to clarify the role of gut microbiota in the anti-diabetic activity of BK extract. MATERIALS AND METHODS: High fat diet combined with low-dose streptozotocin (45 mg/kg) was used to establish a T2D rat model, and the body weight of rats was measured every five days. Fasting blood glucose (FBG), glycosylated serum protein (GSP), insulin resistance index (HOMA-IR), insulin sensitivity index (ISI), lipopolysaccharide (LPS), and three inflammatory factors (TNF-α, IL-1 ß and IL-6) were measured to evaluate the anti-diabetic activity of BK. Moreover, pseudo-germ-free animals were prepared by oral administration of an antibiotic mixture (100 mg/kg neomycin, 100 mg/kg ampicillin and 50 mg/kg metronidazole) twice per day for 6 days to assess the role of gut microbiota. Gut microbiota analysis was performed through 16S rRNA high-throughput sequencing method. RESULTS: After 30 days of administration, BK extract could significantly decrease the levels of body weight, FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1ß and IL-6, and increase ISI levels in T2D rats. However, when the gut microbiota of T2D rats was disturbed by antibiotics, BK could not improve HOMA-IR and ISI levels in T2D rats. The results indicated that the anti-diabetic effect of BK might depend on the gut microbiota. Moreover, sequencing of 16S rRNA genes demonstrated that BK could significantly improve the gut microbiota disorder of T2D rats. Specifically, BK increased the abundance of phyla Bacteroidetes and genera Akkermansia and the ratio of Bacteroides/Firmicutes, while reducing the abundance of phyla Proteobacteria and genera Collinella, [Ruminococcus]_gauvreauii_Group, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella, and Prevotella_9 in T2D rats. Additionally, correlation analysis revealed that Akkermansia was positively correlated with ISI, while [Ruminococcus]_gauvreauii_Group, Collinella, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella and Prevotella_9 were positively correlated with FBG, GSP, LPS, HOMA-IR, TNF-α, IL-1ß, and IL-6. CONCLUSION: BK extract has a good anti-diabetic effect on T2D rats. The mechanism by which this extract exerts its action is, at least partly, related to its regulation of gut microbiota.

Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence.

The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide. It is of great significance to find effective drugs from natural compounds to treat metabolic diseases. Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, exists in many traditional medicinal plants. In recent years, BBR has received widespread attention due to its good potential in the treatment of metabolic diseases. In order to promote the basic research and clinical application of BBR, this review provides a timely and comprehensive summary of the pharmacological and clinical advances of BBR in the treatment of five metabolic diseases, including type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease, hyperlipidemia, and gout. Both animal and clinical studies have proved that BBR has good therapeutic effects on these five metabolic diseases. The therapeutic effects of BBR are based on regulating various metabolic aspects and pathophysiological procedures. For example, it can promote insulin secretion, improve insulin resistance, inhibit lipogenesis, alleviate adipose tissue fibrosis, reduce hepatic steatosis, and improve gut microbiota disorders. Collectively, BBR may be a good and promising drug candidate for the treatment of metabolic diseases. More studies, especially clinical trials, are needed to further confirm its molecular mechanisms and targets. In addition, large-scale, long-term and multi-center clinical trials are necessary to evaluate the efficacy and safety of BBR in the treatment of these metabolic diseases.

Efficacy and safety of total glucosides of paeony for rheumatoid arthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by erosion of joints and surrounding tissues. RA not only causes the decline of patients' physical function and quality of life, but also brings huge economic burden to patients' families and society. Total glucosides of paeony (TGP) is commonly used in treating RA in China. At present, there are many clinical reports about this medicine, but these reports have their own flaws. Therefore, there is an urgent need for systematic review and meta-analysis of the existing clinical evidence. METHODS AND ANALYSIS: Literature search will be carried out in 6 databases, and the literatures will be screened according to the inclusion and exclusion criteria. The clinical effective rate will be taken as primary outcome. Serum rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, Western Ontario and McMaster before and after treatment and adverse effects will be secondary outcomes. The heterogeneity of the study will be examined by χ and I test. To identify the source of heterogeneity, subgroup analysis will be carried out. The sensitivity test will be conducted investigate the stability of results. Funnel plot and Egger test will be used to evaluate publication bias. Finally, the quality of evidence will be summarized. RESULTS: The results will be published in peer-reviewed journals. CONCLUSIONS: This study will systematically evaluate the efficacy of TGP in the treatment of RA. The results of this study can better guide clinical practice. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/85QVF.

Anti-Diabetic Effects of Berberis kansuensis Extract on Type 2 Diabetic Rats Revealed by 1 H-NMR-Based Metabolomics and Biochemistry Analysis.

The dried stem bark of Berberis kansuensis C.K.Schneid. (Berberidaceae) was widely used to treat diabetes in traditional Tibetan medicine system. However, its anti-diabetic mechanisms have not been elucidated. In this study, 1 H-NMR-based metabolomics combined with biochemistry assay was applied to investigate the anti-diabetic activities as well as underlying mechanisms of B. kansuensis extract on type 2 diabetic rats. The results showed that after 30 days treatment with B. kansuensis extract, the levels of FBG, GSP, INS, TNF-α, IL-1ß and IL-6 were significantly decreased in B. kansuensis group compared with the model group. Besides, a total of 28 metabolites were identified in rat serum by 1 H-NMR-based metabolomics method, 16 of which were significantly different in the normal group compared with the model group, and eight of them were significantly reversed after B. kansuensis intervention. Further analysis of metabolic pathways indicated that therapeutic effect of B. kansuensis might be predominantly related to their ability to improve glycolysis and gluconeogenesis, citric acid cycle, lipid metabolism, amino acid metabolism and choline metabolism. The results of both metabolomics and biochemical analysis indicated that B. kansuensis extract has a potential anti-diabetic effect on type 2 diabetic rats. Its therapeutic effect may be based on the ability of anti-inflammation, alleviating insulin resistance and restoring several disturbed metabolic pathways.

1H NMR-Based Metabolomics Coupled With Molecular Docking Reveal the Anti-Diabetic Effects and Potential Active Components of Berberis vernae on Type 2 Diabetic Rats.

The dried stem bark of Berberis vernae C.K.Schneid., known as "Xiao-bo-pi" in Chinese, is a representative anti-diabetic herb in traditional Tibetan medical system. However, its anti-diabetic mechanisms and active components remain unclear. In this study, 1H NMR-based metabolomics, biochemistry assay, molecular docking, and network analysis were integrated to evaluate the anti-diabetic effects of B. vernae extract on type 2 diabetic rats, and to explore its active components and underlying mechanisms. Diabetes was induced by high-fat diet and streptozotocin. After 30 days of treatment, B. vernae extract significantly decreased the serum levels of fasting blood glucose, insulin, insulin resistance index, glycated serum protein, TNF-α, IL-1ß, and IL-6, whereas significantly increased the serum levels of insulin sensitivity index in type 2 diabetic rats. A total of 28 endogenous metabolites were identified by 1H NMR-based metabolomics, of which 9 metabolites that were changed by diabetes were significantly reversed by B. vernae extract. The constructed compound-protein-metabolite-disease (CPMD) interaction network revealed the correlation between chemical constituents, target proteins, differential metabolites, and type 2 diabetes. Ferulic acid 4-O-ß-D-glucopyranoside, bufotenidine, jatrorrhizine, and berberine showed good hit rates for both the 30 disease-related proteins and 14 differential metabolites-related proteins, indicating that these four compounds might be the active ingredients of B. vernae against type 2 diabetes. Moreover, pathway analysis revealed that the anti-diabetic mechanisms of B. vernae might be related to its regulation of several metabolic pathways (e.g., butanoate metabolism) and disease-related signal pathways (e.g., adipocytokine signaling pathway). In summary, B. vernae exerts a significant anti-diabetic effect and has potential as a drug candidate for the treatment of type 2 diabetes.

The multiple organs insult and compensation mechanism in mice exposed to hypobaric hypoxia.

This study was first and systematically conducted to evaluate the hypoxia response of the brain, heart, lung, liver, and kidney of mice exposed to an animal hypobaric chamber. First, we examined the pathological damage of the above tissues by Hematoxylin & eosin (H&E) staining. Secondly, biochemical assays were used to detect oxidative stress indicators such as superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG). Finally, the hypoxia compensation mechanism of tissues was evaluated by expression levels of hypoxia-inducible factor 1 alpha (HIF-1α), erythropoietin (EPO), and vascular endothelial growth factor (VEGF). During the experiment, the mice lost weight gradually on the first 3 days, and then, the weight loss tended to remain stable, and feed consumption showed the inverse trend. H&E staining results showed that there were sparse and atrophic neurons and dissolved chromatin in the hypoxia group. And hyperemia occurred in the myocardium, lung, liver, and kidney. Meanwhile, hypoxia stimulated the enlargement of myocardial space, the infiltration of inflammatory cells in lung tissue, the swelling of epithelial cells in hepatic lobules and renal tubules, and the separation of basal cells. Moreover, hypoxia markedly inhibited the activity of SOD and GSH and exacerbated the levels of MDA and GSSG in the serum and five organs. In addition, hypoxia induced the expression of HIF-1α, EPO, and VEGF in five organs. These results suggest hypoxia leads to oxidative damage and compensation mechanism of the brain, heart, lung, liver, and kidney in varying degrees of mice.

Identification of drought-responsive miRNAs in Hippophae tibetana using high-throughput sequencing.

MicroRNAs (miRNAs) play an important role in abiotic stress response in plants. However, the total miRNA profiles (miRNome) and drought-responsive miRNAs in H. tibetana have not been identified. In this study, we present the first report on the miRNome profiles of H. tibetana by high-throughput sequencing technology. 116 known and 4 predicted novel miRNAs were all identified in six H. tibetana samples. Moreover, to reveal the drought-responsive miRNAs in H. tibetana, we compared the miRNA profiles of H. tibetana grown under water sufficiency and drought stress. The results showed that 39 known miRNAs were up-regulated, while 34 miRNAs were downregulated under drought stress. Moreover, the expression of two novel miRNAs (novel_mir_24 and novel_mir_87) showed notable changes in response to drought stress. The target genes of these differentially expressed miRNAs were mainly enriched in cellular process, metabolic process, cell part, and response to stimulus. The identified drought-responsive miRNAs might be used for improving drought tolerance in H. tibetana and other plateau plants.

Magnoflorine: A review of its pharmacology, pharmacokinetics and toxicity.

Magnoflorine is an important quaternary aporphine alkaloid that is isolated from some commonly used herbal medicines (e.g., Sinomenium acutum (Thunb.) Rehder & E.H.Wilson and Coptis chinensis Franch.). In recent years, magnoflorine has received increasing attention due to its multiple pharmacological activities. This review provides the first comprehensive summary of the plant sources, pharmacological effects, toxicity, and pharmacokinetic characteristics of magnoflorine. The results indicated that magnoflorine possesses a wide spectrum of pharmacological properties, including anti-diabetic, anti-inflammatory, neuropsychopharmacological, immunomodulatory, hypotensive, antioxidant, and antifungal activities. Pharmacokinetic studies have shown that magnoflorine has low bioavailability and high absorption and elimination rates. However, the other compounds (e.g., berberine) present in herbal medicines could reduce the absorption and removal rates of magnoflorine and increase its bioavailability. Moreover, toxicity studies have suggested that magnoflorine is non-toxic to most cells. However, long-term and high-dose toxicity testing in animals is still lacking. In view of good pharmacological activities, magnoflorine is expected to be a potential drug candidate for the treatment of diabetes, depression, or Alzheimer's disease. However, further studies are needed to elucidate its molecular mechanisms and targets, clarify its toxicity, and improve its oral bioavailability.

Brassica rapa Polysaccharides Ameliorate CCl4 -Induced Acute Liver Injury in Mice through Inhibiting Inflammatory Apoptotic Response and Oxidative Stress.

Brassica rapa L., also called NIUMA, is used empirically in Tibetan medicine for its antioxidant, anti-inflammatory and antiradiation activities. This study explored the hepatoprotective effects of B. rapa polysaccharides (BRPs) on acute liver injury induced by carbon tetrachloride (CCl4 ) in mice and the underlying mechanisms. Mice were treated with CCl4 after the oral administration of BRPs (55, 110 and 220 mg/kg) or bifendate (100 mg/kg) for 7 days. Blood and liver samples of mice were collected for analysis after 24 h. The ALP, ALT and AST levels and the biological activities of SOD, MDA and GSH-Px were measured. Histopathological changes in the liver were determined through hematoxylin and eosin staining. Moreover, TNF-α, IL-1ß and IL-6 expression levels were detected by commercial reagent kits. Finally, Western blot analysis was used to check the relative expression levels of caspase-3, p-JAK2 and p-STAT3. The BRP pre-treatment significantly decreased the enzymatic activities of ALT, ALP and AST in the serum, markedly increased the activities of SOD and GSH-Px in the liver and reduced the MDA concentration in the liver. BRPs alleviated hepatocyte injury and markedly inhibited the expression of TNF-α, IL-1ß and IL-6, also downregulating the CCl4 -induced hepatic tissue expression of caspase-3. Furthermore, BRPs inhibited the JAK2/STAT3 signaling pathway in a dose-dependent manner in the liver. This study demonstrated that BRPs exert hepatoprotective effect against the CCl4 -induced liver injury via modulating the apoptotic and inflammatory responses and downregulating the JAK2/STAT3 signaling pathway. Therefore, B. rapa could be considered a hepatoprotective medicine.

Fecal medicines used in traditional medical system of China: a systematic review of their names, original species, traditional uses, and modern investigations.

In China, the medical use of fecal matter (fresh fecal suspension or dry feces) can be dated back to the fourth century, approximately 1700 years ago. In long-term clinical practice, Chinese doctors have accumulated unique and invaluable medical experience in the use of fecal materials. In view of their good curative effect and medicinal potential, fecal medicines should be paid much attention. This study aimed to provide the first comprehensive data compilation of fecal medicines used in various Chinese traditional medical systems by bibliographic investigation of 31 medicine monographs and standards. A total of 54 fecal medicines were found to be used in 14 traditional Chinese medical systems. Their names, original species, medicinal forms, and traditional uses were described in detail. These fecal medicines were commonly used to treat gastrointestinal, nervous system, skin, and gynecological diseases. Commonly used fecal medicines include Wu-Ling-Zhi, Jiu-Fen and Hei-Bing-Pian. The information summarized in this study can provide a good reference for the development and utilization of fecal medicines. Further studies are necessary to prove their medicinal value, identify their active ingredients, and elucidate their mechanisms of action so that more people can accept these special medicines.

Antistress Effects of San-Huang-Xie-Xin Decoction on Restraint-Stressed Mice Revealed by 1H NMR-Based Metabolomics and Biochemistry Analysis.

San-Huang-Xie-Xin decoction (SHXXD), composed of Rhei Radix et Rhizoma, Coptidis Rhizoma, and Scutellariae Radix, is a representative antipyretic and detoxifying prescription in traditional Chinese medicine. In this study, we investigated the antistress effects and underlying mechanisms of San-Huang-Xie-Xin decoction (SHXXD) on restraint-stressed mice by 1H NMR-based metabolomics combined with biochemistry assay. A total of 48 male mice (5 weeks old, 18-22 g) were divided randomly into 6 groups (n = 8), including the normal group, restraint-stressed group, vitamin C group (positive drug, 17 mg/kg), and 3-dosage groups of SHXXD (200, 400, and 800 mg/kg). The stress model was induced by restraining mice in a polypropylene centrifuge tube for 6 h every day. The rotarod test was performed, and several biochemical indicators were measured. Moreover, other 24 animals were divided into 3 groups (n = 8) including the normal group, restraint-stressed group, and SHXXD group (800 mg/kg) for 1H NMR-based metabolomics analysis. Our results showed that SHXXD significantly increased the rotarod time, thymus index, spleen index, and the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and interleukin- (IL-) 2, but decreased the levels of malondialdehyde (MDA), IL-1ß, tumor necrosis factor- (TNF-) α, corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in restraint-stressed mice. Moreover, the contents of eight endogenous metabolites that were changed by restraint stress were significantly reversed by SHXXD. The results of both metabolomics and biochemical analysis indicated that SHXXD (800 mg/kg, p.o.) could improve the biochemical changes and metabolic disorders in restraint-stressed mice by antioxidation and anti-inflammation, enhancing the body's immune function and restoring several disturbed metabolic pathways (i.e., lipid metabolism, glycolysis and gluconeogenesis, inflammatory injury, and energy metabolism). Taken together, these results indicated that SHXXD has a potential antistress effect in restraint-stressed mice and could be considered as a candidate drug for stress-related disorders.

Rhodiola crenulata attenuates apoptosis and mitochondrial energy metabolism disorder in rats with hypobaric hypoxia-induced brain injury by regulating the HIF-1α/microRNA 210/ISCU1/2(COX10) signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata, a traditional Tibetan medicine, has shown promise in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, the underlying mechanisms remain unclear. This study investigated the protective effects of R. crenulata aqueous extract (RCAE) on HH-induced brain injury in rats. MATERIALS AND METHODS: An animal model of high-altitude hypoxic brain injury was established in SD rats using an animal decompression chamber for 24 h. Serum and hippocampus levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were then determined using commercial biochemical kits. Neuron morphology and vitality were also evaluated using H&E and Nissl staining, and TUNEL staining was used to examine apoptosis. Gene and protein expression of HIF-1α, microRNA 210, ISCU1/2, COX10, Apaf-1, cleaved Caspase-3, Caspase-3, Bax, Bcl-2, and Cyto-c were determined by western blot, immunohistochemical and qRT-PCR analysis. RESULTS: RCAE administration attenuated HH-induced brain injury as evidenced by decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, improvements in hippocampus histopathological changes, increased cell vitality and ATP level, and reduced apoptotic cell numbers. RCAE treatment also enhanced HIF-1α, ISCU1/2, COX10, and Bcl-2 protein expression, while dramatically inhibiting expression of Apaf-1, Bax, Cyto-c, and cleaved Caspase-3. Treatment also increased gene levels of HIF-1α, microRNA 210, ISCU1/2, and COX10, and decreased Caspase-3 gene production. CONCLUSIONS: RCAE attenuated HH-induced brain injury by regulating apoptosis and mitochondrial energy metabolism via the HIF-1α/microRNA 210/ISCU1/2 (COX10) signaling pathway.

Establishment and evaluation of a simulated high­altitude hypoxic brain injury model in SD rats.

This study was conducted to establish a stable hypobaric hypoxia brain injury model. SD rats were randomly separated into control and model groups, and placed outside or inside of a hypobaric chamber, respectively. Subsequent to 24 h anoxic exposure, plasma superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) and lactate dehydrogenase (LDH) were measured using commercial biochemical kits. Hematoxylin­eosin (H&E), Nissl's and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to observe the morphology of neurons in the hippocampus. The protein expression levels of apoptotic protease activating factor­1 (Apaf­1), hypoxia inducible factor­1α (HIF­1α), caspase­3, cleaved caspase­3, Bcl­2­associated X protein (Bax) and cytochrome c (cyto­c) were detected using western blot and immunohistochemistry analyses. Hypoxic substantially induced morphological lesions in the hippocampus concomitant with the physical behavioral performance deficit. Furthermore, hypoxia markedly exacerbated the levels of MDA, LDH and GSSG, and restrained GSH (P<0.01) and SOD (P<0.05) levels compared with the control group. In addition, hypoxia significantly induced the protein expression of Apaf­1, HIF­1α, caspase­3, cleaved caspase­3, Bax and Cyto­c (P<0.01) compared with the control group. Finally, a lower number and volume of Nissl bodies were verified in the hypoxic group. TUNEL results demonstrated a greater number of apoptotic cells in the hypoxic group. The present study demonstrates a model of rat hypoxic brain injuries induced by a hypobaric chamber at 9,000 m for 24 h. Furthermore, the redox enzyme, HIF­1α and mitochondrial apoptosis­associated protein, along with H&E and Nissl's staining, may be applied to evaluate the degree of injury.