Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. In our previous in vivo study, an interaction between stilbenes and anthraquinones has been discovered and a hypothesis is proposed that the interaction between stilbene glucoside-enriching fraction and emodin may contribute to the side effects of PMR. To further support our previous in vivo results in rats, the present in vitro study was designed to evaluate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) on the cellular absorption and human liver microsome metabolism of emodin. The obtained results indicated that the absorption of emodin in Caco-2 cells was enhanced and the metabolism of emodin in human liver microsomes was inhibited after TSG treatment. The effects of the transport inhibitors on the cellular emodin accumulation were also examined. Western blot assay suggested that the depressed metabolism of emodin could be attributed to the down-regulation of UDP-glucuronosyltransferases (UGTs) 1A8, 1A10, and 2B7. These findings definitively demonstrated the existence of interaction between TSG and emodin, which provide a basis for a better understanding of the underlying mechanism for PMR-induced liver injury.
Caco-2 Cells ; Chemical and Drug Induced Liver Injury ; etiology ; Emodin ; analysis ; metabolism ; Fallopia multiflora ; adverse effects ; Glucosides ; toxicity ; Glucuronosyltransferase ; antagonists & inhibitors ; Humans ; Plant Roots ; Stilbenes ; toxicity

Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.
Aconitum ; adverse effects ; chemistry ; toxicity ; Alkaloids ; adverse effects ; analysis ; toxicity ; Animals ; Cardiovascular Agents ; adverse effects ; chemistry ; standards ; toxicity ; Desiccation ; methods ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; standards ; toxicity ; Male ; Maximum Tolerated Dose ; Plant Roots ; chemistry ; Rats, Sprague-Dawley ; Technology, Pharmaceutical ; methods

Chuanwu (CW), a famous traditional Chinese medicine (TCM) from the mother roots of Aconitum carmichaelii Debx.. (Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao (Radix Glyeyrrhizae, CG), Baishao (Radix Paeoniae Alba, CS) and Ganjiang (Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.
Aconitum ; toxicity ; Animals ; Biomarkers ; urine ; Chromatography, High Pressure Liquid ; methods ; Drug-Related Side Effects and Adverse Reactions ; metabolism ; prevention & control ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; toxicity ; Ginger ; Glycyrrhiza uralensis ; Heart ; Inactivation, Metabolic ; Liver ; Male ; Mass Spectrometry ; methods ; Medicine, Chinese Traditional ; Metabolome ; Metabolomics ; Paeonia ; Plant Roots ; Rats, Wistar ; Rhizome

The diarrheal rat model was established by orally administering senna. The preventive experiment was concurrent for 6 days. The treatment experiment modeling had lasted for 12 days. The administration started at the 7th day, and lasted for 6 days. During the experiment, efforts were made in symptom score and weighing. After the experiment, hearts, livers, spleens, kidneys, brains, adrenals and thymuses were collected and weighed, lactic dehydrogenase (LDH) and cardiac troponin-I (cTn-I) in serum were detected. The efficacy of aqueousextracts from Aconiti Lateralis Radix Praeparata in preventing and treating rats with diarrheal and its accompanying toxicity were respectively studied. The result shows that aqueous extracts from Aconiti Lateralis Radix Praeparata could improve syndromes of rats with diarrheal. The 50% effective doses (ED50) of preventive and treatment administrations were 1.420 4 g · kg(-1) and 1.048 9 g · kg(-1), respectively. Aqueous extracts from Aconiti Lateralis Radix Praeparata could decrease the ratio of heart to body weight, and increase serum LDH and cTn-I. It was concluded that aqueous extracts from Aconiti Lateralis Radix Praeparata had a specific preventive and treatment effect on rats with diarrheal caused by senna, but with specific toxicity on heart.
Aconitum ; adverse effects ; chemistry ; Animals ; Body Weight ; drug effects ; Diarrhea ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Heart ; drug effects ; Humans ; Male ; Plant Roots ; adverse effects ; chemistry ; Rats ; Rats, Wistar ; Spleen ; drug effects

The roots of Angelica sinensis (RAS), are a Chinese herbal medicine traditionally used in prescriptions for replenishing blood, treating abnormal menstruation, and other women's diseases. It has also been widely marketed as health food for women's care in Asia, and as a dietary supplement in Europe and America. RAS is well-known for its hematopoietic, antioxidant, and immunoregulatory activities. RAS also possesses anti-cancer, memory, radioprotective, and neuroprotective effects. Phytochemical investigations on this plant led to organic acids, phthalides, polysaccharides, and other metabolites. Based on recent animal studies and clinical trials, RAS has been used in the treatment of gynecologic diseases, cardio-cerebrovascular disease, nervous system diseases, and nephrotic syndrome. In this review, the recent phytochemical and pharmacological studies, drug-drug interactions, clinical applications, and toxicity of RAS are summarized.
Angelica sinensis ; adverse effects ; chemistry ; Animals ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; pharmacology ; Humans ; Phytotherapy ; Plant Roots ; chemistry

AIM: Euphorbia kansui (E. KS) is a traditional medicine used in China for thousands of years with the effect of propulsion in the gastrointestines. However, there is no reported study of E. KS on gastrointestinal motility until now. The aim of this work is to study the effect of E. KS on the propulsion of gastrointestines, and to elucidate the possible mechanism of action. METHODS: E.KS was prepared as a 30% ethanol extract and used for the experiment of small and large intestines of mice by oral administration with three different dosages (1.2, 0.6 and 0.3 g·kg(-1)). The feces were observed in vivo. The morphology was carried out to detect if there are any changes in the intestines after the extract of E. KS administration. The assays of mRNA and protein expression were employed to observe IL-1β, TNFα and caspase 3. RESULTS: It was shown that the extract of E.KS promoted diarrhea in mouse feces after administration, inhibited the contraction of smooth muscle of mouse small intestine and caused the inflammatory exudation on the mucosa of the intestines, enhanced the expression of both mRNA and the protein levels of IL-1β and TNFα in the small or large intestines. CONCLUSION The results showed that the extract of E. KS acted on the intestinal smooth muscle with propulsion of feces involving the irritation of the intestines with acute inflammatory reactions.
Animals ; Diarrhea ; etiology ; genetics ; immunology ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Euphorbia ; adverse effects ; chemistry ; Female ; Gastrointestinal Motility ; drug effects ; Humans ; Interleukin-1beta ; genetics ; immunology ; Intestines ; drug effects ; physiopathology ; Male ; Mice ; Mice, Inbred ICR ; Muscle, Smooth ; drug effects ; physiopathology ; Plant Roots ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVETo assess the in-vitro antibacterial activity and anti-inflammatory activity of orally administered different extracts (Hydro-alcoholic, methanolic, ethyl acetate and hexane) of Rauvolfia tetraphylla (R. tetraphylla) root bark in Carrageenan induced acute inflammation in rats.

METHODSIn-vitro antibacterial activity was evaluated for extracts against four Gram positive and four Gram negative bacteria by using cylinder plate assay. Hydro-alcoholic extract (70% v/v ethanol) at 200, 400 and 800 mg/kg doses and methanolic, ethyl acetate and hexane extracts at doses 100, 200 and 400 mg/kg were tested for anti-inflammatory activity in Carrageenan induced rat paw oedema model and paw thickness was measured every one hour up to 6 hrs.

RESULTSAll extracts of R. tetraphylla root bark showed good zone of inhibition against tested bacterial strains. In Carrageenan induced inflammation model, hydro-alcoholic and methanolic extract of R. tetraphylla root bark at three different doses produced significant (P<0.001) reduction when compared to vehicle treated control group and hexane, ethyl acetate extracts.

CONCLUSIONSIn the present study extracts of R. tetraphylla root bark shows good in-vitro antibacterial activity and in-vivo anti-inflammatory activity in rats.

Animals ; Anti-Bacterial Agents ; pharmacology ; Anti-Inflammatory Agents ; pharmacology ; Bacteria ; drug effects ; Carrageenan ; adverse effects ; Disease Models, Animal ; Edema ; chemically induced ; drug therapy ; Female ; Male ; Microbial Sensitivity Tests ; Plant Bark ; chemistry ; Plant Extracts ; pharmacology ; Plant Roots ; chemistry ; Rats ; Rauwolfia ; chemistry

AIM: To observe the anti-oxidative activity and adverse laxative effect of raw, traditional processed and fermented products of Polygoni Multiflori Radix (PMR), and furthermore, to evaluate the fermentation method used in the processing procedure of PMR. METHODS: In vitro ferric reducing antioxidant power (FRAP) assay was carried out to evaluate the anti-oxidative activity. Modulation of normal defecation and effect on gastrointestinal motility in mice were carried out to investigate their adverse laxative effect. RESULTS: Fermented PMR induced less severe laxative adverse effect than Polygoni Multiflori Radix Praeparata (PMRP). PMR fermented with Rhizopus sp. (FB) could modulate the defecation significantly. The gastrointestinal motility was inhibited by PMRP and PMR fermented with Rhizopus oryzae (FA). FA and FB showed better antioxidant activity than PMRP in 50% and 95% ethanol group. Contents of 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) were reduced significantly after traditional processing but maintained after fermentation. Emodin and physcion were increased after traditional processing and fermented with Rhizopus oryzae. CONCLUSION All processing procedure, including fermentation, might reduce its anti-oxidative activity. However, most of the processed products could lessen the adverse effect on gastrointestinal tract compared to PMR. Fermentation with Rhizopus oryzae was considered as a promising processing method of PMR.
Animals ; Antioxidants ; pharmacology ; Defecation ; drug effects ; Emodin ; adverse effects ; analogs & derivatives ; pharmacology ; Female ; Fermentation ; Gastrointestinal Motility ; drug effects ; Gastrointestinal Tract ; drug effects ; Laxatives ; adverse effects ; Male ; Mice ; Mice, Inbred Strains ; Plant Extracts ; adverse effects ; pharmacology ; Plant Roots ; chemistry ; Polygonum ; adverse effects ; chemistry ; Rhizopus

OBJECTIVETo study the changes of mucosa irritation of crude and processed Radix Phytolaccae.

METHODGastrointestinal experiments on rats and mice and the rabbits' eyes irritation experiments were applied to investigate the changes of mucosa irritation of crude and processed Radix Phytolaccae.

RESULTThe mucosa irritation of processed Radix Phytolaccae decreased obviously compared to crude one.

CONCLUSIONAfter being processed with vinegar, the mucosa irritation on Radix Phytolaccae decreased obviously.

Acetic Acid ; chemistry ; Animals ; Dinoprostone ; metabolism ; Drug Compounding ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; Eye ; drug effects ; Gastric Mucosa ; drug effects ; metabolism ; Male ; Mice ; Phytolacca ; chemistry ; Plant Roots ; chemistry ; Rats

OBJECTIVETo observe the effects of Colquhounia root tablet (CRT) combined with immunosuppressive protocal in treating patients with chronic allograft nephropathy (CAN).

METHODSThirty-three patients of CAN, with urinary protein > or = 1.0 g/24 h and serum creatinine (SCr) > or =150 (micromol/L), were assigned to two groups, the 15 in the treated group treated with CRT combining modified immunosuppressive protocol (IIP) therapy and the 18 in the control group treated with IIP alone, all for 6 months. The clinical efficiency, 24 h urinary protein and clearance of creatinine (CCr) were observed.

RESULTSThe effective rate in the treated group [60% (9/15 cases)] was significantly higher than that in the control group [22.0% (4/18 cases), P < 0.05], and the lowering of 24 h urinary protein in the former was more significant than in the latter at the end of the 3rd and the 6th month of treatment (P < 0.05). At the end of 12-month follow-up, SCr and CCr level were stable in the treated group, while in the control group, SCr level increased and CCr level decreased significantly (P < 0.05), comparisons of the two indexes between the two groups at the end of the therapeutic course and follow-up study all showed significant differences (P < 0.05). Serum creatinine doubling to baseline were seen in 2 patients of the treated group and 7 of the control group. One patient in the treated group and 4 in the control group entered the end stage of renal disease.

CONCLUSIONTherapy with CRT combined IIP seems to be more effective in reducing urinary protein excretion in patients with CAN than that with IIP alone, and a more favorable renal function preserving effect of the former is shown by a short-term follow-up.

Adult ; Aged ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Diseases ; drug therapy ; immunology ; surgery ; Kidney Transplantation ; adverse effects ; Lamiaceae ; chemistry ; Male ; Middle Aged ; Plant Roots ; chemistry ; Transplantation, Homologous ; adverse effects ; Young Adult