Acute hepatotoxicity and nephrotoxicity risk assessment of the Tibetan medicine 25 flavors of the turquoise pill based on 1H-NMR metabonomics.

ETHNOPHARMACOLOGICAL RELEVANCE: 25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. AIM OF THE STUDY: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. MATERIALS AND METHODS: The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. RESULTS: The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. CONCLUSION: Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Therapeutic assessment of fractions of Gastrodiae Rhizoma on chronic atrophic gastritis by 1H NMR-based metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY: To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS: The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS: The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

Potential hepatoxicity risk of the shell of Herpetospermum caudigerum Wall in rats based on 1H-NMR metabonomics.

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

Hepatoprotection of Herpetospermum caudigerum Wall. against CCl4-induced liver fibrosis on rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk. AIM OF THE STUDY: Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end. This study aims to demonstrate the protective effect of HCW against CCl4-induced liver injury in rats and to explore the underlying mechanisms. MATERIALS AND METHODS: Hepatic fibrosis was induced by intraperitoneal injection of CCl4. Liver function markers, fibrosis markers, serum anti-oxidation enzymes as well as elements levels were determined. Serum and liver tissues were subjected to NMR-based metabolomics and multivariate statistical analysis. RESULTS: HCW could significantly reduce the elevated levels of fibrosis markers such as hyaluronidase, laminin, Type III procollagen and Type IV collagen in the serum, improve the activities of the antioxidant enzymes, and effectively reverse the abnormal levels of elements in liver fibrosis rats. Correlation network analysis revealed that HCW could treat liver fibrosis by ameliorating oxidative stress, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. CONCLUSION: This integrated metabolomics approach confirmed the validity of the traditional use of HCW in the treatment of liber fibrosis, providing new insights into the underlying mechanisms.

Nuclear magnetic resonance-based metabolomics approach to evaluate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.

Hepatotoxicity and hepatoprotection of Polygonum multiflorum Thund. as two sides of the same biological coin.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thund., a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating hypertension, hyperlipidemia, premature graying of hair, and etc., has aroused wide concern for its reported potential liver toxicity. Due to its various active ingredients, the mechanisms underlying the hepatotoxicity of raw Polygonum multiflorum Thund (RPM) remain largely unknown. AIM OF THE STUDY: 1H NMR metabolomics was used to study the mechanism of RPM induced hepatotoxicity and disclosed the existence of hepatotoxicity and hepatoprotection conversion during RPM administration in mice. MATERIALS AND METHODS: Three dosages of RPM were administered by gavage to mice for consecutive 28 days. The serum and liver samples were collected and then subjected for histopathology observation, biochemical measurement and 1H NMR metabolic profiling. RESULTS: RPM caused oxidative stress and mitochondria dysfunction in mice, resulting in significant disturbance in energy metabolism, amino acid metabolism and pyrimidine metabolism and also inducing inflammatory responses. RPM induced hepatotoxicity in an apparent non-linear manner: the most severe in low dosage group, and to a less extent in medium group according to metabolomics analysis. The attenuation of liver injury in mice livers might result from the therapeutic effects, such as anti-oxidative capacity of RPM components. CONCLUSION: RPM exerted a complicated non-linear manner in healthy recipients, switching between hepatoxicity and hepatoprotection dependent on the dosage and status of the body.

Protective effects of Polygonum multiflorum on ischemic stroke rat model analysed by 1H NMR metabolic profiling.

Stroke is the third most common cause of death in most industrialized countries. Polygonum multiflorum (He-Shou-Wu, HSW) is one of the traditional Chinese medicines with multiple pharmacological activities which is widely used in Chinese recipe. This study aims to explore the protective effect of HSW on ischemic stroke rat model and to elucidate the underlying mechanisms. The mortality rate, neurological deficit, cerebral infarct size, histopathology, immunohistochemistry, biochemical parameters, quantitative real-time polymerase chain reaction and western blotting were used to access the treatment effects of HSW on ischemic stroke. Proton nuclear magnetic resonance (1H NMR) based metabolomics analysis disclosed that HSW could relieve stroke rats suffering from the ischemia/reperfusion injury by ameliorating the disturbed energy and amino acids metabolisms, alleviating the oxidative stress from reactive oxygen species and reducing the inflammation. HSW treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 signaling pathway, and exert anti-inflammatory effect by decreasing the levels of inflammatory factors such as cyclooxygenase-2, interleukin-1ß, interleukin-6 and tumor necrosis factor-α. The integrated metabolomics approach showed its potential in understanding mechanisms of HSW in relieving ischemic stroke. Further study to develop HSW as an effective therapeutic agent to treat ischemic stroke is warranted.