The extraction, purification, structural features, bioactivities, and applications of Schisandra chinensis polysaccharides: A review.

Schisandra chinensis, as a famous medicinal and food homologous plant, has a long history of medicinal and dietary therapy. It has the functions of nourishing the kidney, calming the heart, tranquilising the mind, tonifying Qi and producing fluid to relieve mental stress, based on the theory of traditional Chinese medicine. Accumulating evidence has shown that S. chinensis polysaccharides (SCPs) are one of the most important bioactive macromolecules and exhibit diverse biological activities in vitro and in vivo, including neuroprotective, hepatoprotective, immunomodulatory, antioxidant, hypoglycemic, cardioprotective, antitumour and anti-inflammatory activities, etc. This review aims to thoroughly review the recent advances in the extraction and purification methods, structural features, biological activities and structure-activity relationships, potential applications and quality assessment of SCPs, and further highlight the therapeutic potentials and health functions of SCPs in the fields of therapeutic agents and functional food development. Future insights and challenges of SCPs were also critically discussed. Overall, the present review provides a theoretical overview for the further development and utilization of S. chinensis polysaccharides in the health food and pharmaceutical fields.

A comprehensive method for quality evaluation of Tibetan medicine Synotis solidaginea by integrating UHPLC-Q-Orbitrap MS chemical profiling and UHPLC-DAD multi-components quantification.

Synotis solidaginea Hand.-Mazz. (SSD) is a commonly used Tibetan medicinal herb with a long history of therapeutic use and has good medicinal value and development and utilization prospects. This study aimed to establish and validate a comprehensive strategy integrating UHPLC-Q Exactive Orbitrap HRMS chemical profiling and UHPLC-DAD multi-components quantification for the holistic quality evaluation of SSD. Using UHPLC-Q Exactive Orbitrap HRMS, a total of 58 components in SSD including flavonoids, organic acids, terpenoids, coumarin, and alkaloids were identified or tentatively characterized by authentic reference standards and accurate masses and characteristic fragment ions. The proportion of flavonoids and organic acids were the most in SSD. Subsequently, 7 characteristic components in SSD were quantified by a newly established UHPLC-DAD method that was validated in terms of linearity and ranges, LOD and LOQ, precision, repeatability, stability, and accuracy. Finally, the method was successfully used for the quality evaluation of 8 batches of SSD collected from 5 production areas in China. ANOVA and post hoc Tukey test are used to evaluate the differences in component content in SSD from different production areas. There are significant differences in the content of SSD from different regions (P < 0.05), which may be related to the climate, altitude, and other natural environments of the regions. This work laid a valuable foundation for further development and comprehensive quality control of SSD.

Efficacy of acupuncture and pharmacological therapies for vascular cognitive impairment with no dementia: a network meta-analysis.

Background and objective: Vascular cognitive impairment with no dementia (VCIND) is considered to be the prodromal stage of vascular dementia, characterized by insidious onset. Although acupuncture and drug therapies are effective, the optimal therapy for VCIND remains to be further determined. Therefore, we conducted a network meta-analysis to compare the effectiveness of acupuncture therapies and current common medicines for VCIND. Methods: We searched eight electronic databases to identify eligible randomized controlled trials of patients with VCIND treated by acupuncture or drug therapies. The primary outcome was Montreal Cognitive Assessment, and the secondary outcome was Mini-Mental State Examination. We conducted the network meta-analysis within a Bayesian framework. Weighted mean difference with 95% confidence intervals were applied as effect sizes to continuous data for all outcomes. Sensitivity analysis was done to assess the robustness of the findings, and we also carried out a subgroup analysis based on age. We assessed the risk of bias using the Risk of Bias 2.0 tool and applied the Grade of Recommendation Assessment, Development and Evaluation (GRADE) to assess the quality of the outcomes. This study was registered with PROSPERO, number CRD42022331718. Results: A total of 33 studies with 14 interventions were included, including 2603 participants. In terms of the primary outcome, manual acupuncture plus herbal decoction was considered to be the most effective intervention (P = 91.41%), followed by electroacupuncture (P = 60.77%) and manual acupuncture plus piracetam (P = 42.58%), whereas donepezil hydrochloride ranked the least efficacious intervention (P = 54.19%). For the secondary outcome, electroacupuncture plus nimodipine was considered to be the most effective intervention (P = 42.70%), followed by manual acupuncture plus nimodipine (P = 30.62%) and manual acupuncture (P = 28.89%), whereas nimodipine ranked the least efficacious intervention (P = 44.56%). Conclusion: Manual acupuncture plus herbal decoction might be the most effective intervention for VCIND. The combination of acupuncture and drug therapy had a tendency to perform better than monotherapy in terms of clinical outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=331718, identifier: CRD42022331718.

Crataegus pinnatifida: A botanical, ethnopharmacological, phytochemical, and pharmacological overview.

ETHNOPHARMACOLOGICAL RELEVANCE: Crataegus pinnatifida belongs to the Rosaceae family and extensively distribute in North China, Europe, and North America. Its usage was first described in "Xinxiu Ben Cao." The dried fruits of Crataegus pinnatifida Bunge or Crataegus pinnatifida var. major N. E. Br., also known as "Shanzha," is a famous medicine and food homology herb with a long history of medicinal usage in China. C. pinnatifida has the functions for digestive promotion, cardiovascular protection, and lipid reduction. It was traditionally used to treat indigestion, cardiodynia, thoracalgia, hernia, postpartum blood stagnation, and hemafecia. In recent years, C. pinnatifida has attracted worldwide attention as an important medicinal and economical crop due to its multiple and excellent health-promoting effects on cardiovascular, nervous, digestive, endocrine systems, and morbigenous microorganisms of the human body due to its medicinal and nutritional values. AIM OF THE REVIEW: The current review aims to provide a comprehensive analysis of the geographical distribution, traditional usage, phytochemical components, pharmacological actions, clinical settings, and toxicities of C. pinnatifida. Moreover, the connection between the claimed biological activities and the traditional usage, along with the future perspectives for ongoing research on this plant, were also critically summarized. MATERIALS AND METHODS: We collected the published literature on C. pinnatifida using a variety of scientific databases, including Web of Science, ScienceDirect, PubMed, Wiley, Springer, Taylor & Francis, ACS Publications, Google Scholar, Baidu Scholar, CNKI, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations) from 2012 to 2022. RESULTS: In the last decade, over 250 phytochemical compounds containing lignans, phenylpropanoids, flavonoids, triterpenoids, and their glycosides, as well as other compounds, have been isolated and characterized from different parts, including the fruit, leaves, and seeds of C. pinnatifida. Among these compounds, flavonoids and triterpenoids were major bioactive components of C. pinnatifida. They exhibited a broad spectrum of pharmacological actions with low toxicity in vitro and in vivo, such as cardiovascular protection, neuroprotection, anti-inflammatory, antioxidant, antibacterial, antiviral, anti-diabetes, anti-cancer, anti-mutagenic, anti-osteoporosis, anti-aging, anti-obesity, and hepatoprotection and other actions. CONCLUSION: A long history of traditional uses and abundant pharmacochemical and pharmacological investigations have demonstrated that C. pinnatifida is an important medicine and food homology herb, which displays outstanding therapeutic potential, especially in the digestive system and cardiovascular disease. Nevertheless, the current studies on the active ingredients or crude extracts of C. pinnatifida and the possible mechanism of action are unclear. More evidence-based scientific studies are required to verify the traditional uses of C. pinnatifida. Furthermore, more efforts must be paid to selecting index components for quality control research and toxicity and safety studies of C. pinnatifida.

Acupuncture for Hypertension in Animal Models: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to summarize and evaluate the efficacy of acupuncture in hypertension animal study. METHODS: Studies were searched from six databases, including Medline, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, VIP information database, and Chinese Biomedical Literature Database. Study quality of each included study was evaluated according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, and the risk of bias was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were selected as outcomes. Meta-analyses were performed using Stata 12.0 software. The effect size was calculated by combining SBP/DBP/MAP data with the random effects model, respectively. RESULTS: 67 studies containing 1522 animals were included. According to the ARRIVE guideline, 8 items were assessed as poor and 4 items were assessed as excellent. According to the SYRCLE tool, all studies were judged as having high risk of bias. Compared with the hypertension group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. Similarly, compared with the sham-acupuncture group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. CONCLUSION: Although pooled data suggested that the acupuncture group was superior to the hypertension group or sham-acupuncture group for SBP/DBP/MAP, the presentation of poor methodological quality, high risk of bias, and heterogeneity deserves cautious interpretation of the results.

Oral Spermidine Targets Brown Fat and Skeletal Muscle to Mitigate Diet-Induced Obesity and Metabolic Disorders.

INTRODUCTION: Obesity causes many life-threatening diseases. It is important to develop effective approaches for obesity treatment. Oral supplementation with spermidine retards age-related processes, but its influences on obesity and various metabolic tissues remain largely unknow. This study aims to investigate the effects of oral spermidine on brown adipose tissue (BAT) and skeletal muscle as well as its roles in counteracting obesity and metabolic disorders. METHODS AND RESULTS: Spermidine is orally administrated into high-fat diet (HFD)-fed mice. The weight gain, insulin resistance, and hepatic steatosis are attenuated by oral spermidine in HFD-fed mice, accompanied by an alleviation of white adipose tissue inflammation. Oral spermidine promotes BAT activation and metabolic adaptation of skeletal muscle in HFD-fed mice, evidenced by UCP-1 induction and CREB activation in both tissues. Notably, oral spermidine upregulates tyrosine hydroxylase in hypothalamus of HFD-fed mice; spermidine treatment increases tyrosine hydroxylase expression and norepinephrine production in neurocytes, which leads to CREB activation and UCP-1 induction in brown adipocytes and myotubes. Spermidine also directly promotes UCP-1 and PGC-1α expression in brown adipocytes and myotubes. CONCLUSION: Spermidine serves as an oral supplement to attenuate obesity and metabolic disorders through hypothalamus-dependent or -independent BAT activation and skeletal muscle adaptation.

[Effect of timing of acupuncture on limb dysfunction in patients with cerebral infarction: a multicenter prospective cohort pilot study].

OBJECTIVE: To evaluate the clinical efficacy of acupuncture at different timings in acute stage for limb dysfunction in patients with cerebral infarction. METHODS: A total of 101 patients with cerebral infarction limb dysfunction were divided into an early exposure group (n=51) and a late exposure group (n=50) according to the time of first acupuncture treatment during the acute phase. SPSS 25.0 software was used to balance the baseline between the two groups, and 31 pairs of matched patients were included, including 31 cases in the early exposure group and 31 cases in the late exposure group. The two groups were treated with Xingnao Kaiqiao acupuncture at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), Chize (LU 5), Weizhong (BL 40), etc., once a day, and the course of treatment was not limited. In the early exposure group, acupuncture was started after 1 to 3 days of onset; in the late exposure group, acupuncture was started after 11 to 14 days of onset. The modified Rankin scale (mRS) grade was recorded before treatment, 30 and 60 days after onset; Fugl-Meyer assessment (FMA) grade was observed before treatment and 30 days after onset; the effect of acupuncture timing on the patients was analyzed by logistic analysis. RESULTS: Compared before treatment, the mRS grade at 30 and 60 days after onset in the early exposure group was improved (P<0.05), which was superior to the late exposure group (P<0.05); compared before treatment, the FMA grade at 30 days after onset in the early exposure group was improved (P<0.05), which was superior to the late exposure group (P<0.05). The timing of acupuncture was independently correlated with the disability status and the severity of motor dysfunction at 30 days after onset, and the disability status at 60 days after onset (P<0.05). Compared with the late exposure group, the possibility of becoming non-disabled at 30 days after onset (OR=22.882, 95%CI: 4.034-129.778), normal limb motor dysfunction (OR=22.320, 95%CI: 3.454-144.213) and non-disabled at 60 days after onset (OR=8.650, 95%CI: 2.437-30.696) in the early exposure group was increased. CONCLUSION: The timing of acupuncture is an independent factor affecting the disability status and limb motor dysfunction in patients with cerebral infarction, and the effect of early intervention may be better than late intervention.

Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb, Polygonum multiflorum.

The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent "knock-out" and "knock-in" strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4'-tetrahydroxy trans-stilbene-2-O-ß-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization of trans-SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.

Establishment of one-step approach to detoxification of hypertoxic aconite based on the evaluation of alkaloids contents and quality.

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.

Investigation of the chemical markers for experiential quality evaluation of crude aconite by UHPLC-Q-TOF-MS.

J. Sep. Sci. 2016, 39, 4281-4289 DOI: 10.1002/jssc.201600567 Aconite, called tiger and wolf drug, is known in Traditional Chinese Medicine for its strong cardiac effect. In the past, the toxins extracted from aconite were used as arrow poisons to kill animals, hence the name "wolf's bane." To a certain extent, the wolf represents the medicinal characteristics of aconite: fierce, wild and intractable. The cover picture shows, besides the wolf head as the main element, a flow chart of our study and summarizes the main topics of our article.

Investigation of the chemical markers for experiential quality evaluation of crude aconite by UHPLC-Q-TOF-MS.

Many foods and herbs are experientially classified into different commodity grades in commercial circulation. Regarding the hypertoxic herb aconite, large samples are considered to be of better quality. However, this experiential classification lacks a scientific basis. In this study, we focused on the quality diversity among different grades and studied it using the minimum lethal dose assay and a novel ultra high performance liquid chromatography coupled with time-of-flight mass spectrometry method. Toxicity assay result suggested grade I aconite had the lowest toxicity (p < 0.05). Using this method with partial least squares-discriminant analysis, we discovered nine chemomarkers, including neoline, songorine, fuziline, mesaconitine, talatizidine, dexyaconitine, talatisamine, hypaconitine, and fuzitine. Considering their toxicity and activity, we found the levels of toxic ingredients hypaconitine, dexyaconitine, and mesaconitine in grade I were lower than those in grade II (p < 0.01), while the levels of efficacy ingredients songorine, talatisamine, and neoline were the highest in grade I (p < 0.01). Further study demonstrated that the quality variation was associated with plant tissue development and toxic ingredient distribution law. Our results provide scientific evidence for the experiential quality evaluation of aconite, and it will be of great utility for other foods and herbs.

Urine metabolomics study on the liver injury in rats induced by raw and processed Polygonum multiflorum integrated with pattern recognition and pathways analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum L. is a famous traditional Chinese medicine that has always been perceived to be safe. Recently, the increasing case reports on hepatotoxicity induced by Raw P. multiflorum (RP) have attracted particular attention. However, the diagnosis and identification of RP-induced hepatotoxicity are still very difficult for its unknown mechanism and the lack of specific biomarkers. AIM OF THE STUDY: To further explore the toxicity and metabolic mechanisms involved in the hepatotoxicity induced by RP. MATERIALS AND METHODS: The hepatotoxicity induced by RP and its processed products (PP) (dosed at 20g/kg for 4 weeks) on rats were investigated using conventional approaches including the biochemical analysis and histopathological observations. Further, a urinary metabolomic approach was developed to study the metabolic disturbances caused by RP and PP, followed by the pattern recognition approach and pathways analysis. RESULTS: RP showed obvious hepatotoxity whereas PP did not. 16 potential biomarkers (pyridoxamine, 4-pyridoxic acid, citrate et al.) differentially expressed in RP group were identified compared with the control and PP-treated groups. The pathways analysis showed that vitamin B6 metabolism, tryptophan metabolism and citrate cycle might be the major enriched pathways involved in the hepatotoxicity of the herb. CONCLUSION: 16 differentially expressed metabolites were identified to be involved in the RP-induced hepatotoxicity. Vitamin B6 metabolism might be mostly related to the hepatotoxicity induced by RP. This finding may provide a potential therapeutic target or option to treat hepatotoxicity induced by RP.

[Influence of metal ions on stability of 2,3,5,4'-tetrahydroxy stilbene-2-O-ß-D-glucoside contained in Polygoni Multiflori Radix].

Decoction is one of the most commonly used dosage forms of traditional Chinese medicine. The stability of chemical constituents in decoction is closely related to the clinical efficacy and safety. There were few reports about the influence of metal ions in the stability of chemical constituents in traditional Chinese medicine. However, there is no evidence that metal ions in decoction water need to be controlled. In this study, 2,3,5,4'-tetrahydroxy stilbene-2-O-ß-D-glucoside (THSG), one of the main constituents in Polygoni Multiflori Radix was studied. Ordinary tap water, deionized water, and water containing different metal ions were used to investigate and compare the influence on THSG. The results showed that after storage in a dark place at the room temperature for 10 days, the degradation of THSG was 7% in deionized water, while undetectable in tap water. The content of THSG could be decreased by different kinds of metal ions, and the effect was concentration-dependent. Moreover, Fe3+ and Fe2+ showed the greatest influence at the same concentration; and our study has shown that THSG decreased more than 98% in Fe and Fe2+ solutions at 500 ppm concentration. In the same time we found out p-hydroxybenzaldehyde (molecular weight: 122.036 7) and 2,3,5-trihydroxybenzaldehyde-2-O-glycoside (molecular weight: 316.079 4) were the main degradation products of THSG in tap water and water containing Cu2+, Ca2+, Zn2+, Mg2+ and Al3+. The product of THSG dimer with a water molecule was found in water containing Fe3+ and Fe2+. The above results showed that the metal ions in water could significantly influence the stability of THSG in water, indicating that the clinical efficacy and safety of decoction would be affected if the metal ions in water were not under control. It's suggested that deionized water should be used in the preparation of decoction containing Polygoni Multiflori Radix in the clinic to avoid degradation of THSG. Meanwhile, decoction prepared by tap water should be taken by patients in a short time. Our investigation provides important information and reference about the influence of metal ions on the stability of decoctions in other traditional Chinese medicine that have unstable groups such as hydroxyls and unsaturated bonds, etc.

Untargeted Metabolomics Reveals Dose-Response Characteristics for Effect of Rhubarb in a Rat Model of Cholestasis.

Cholestasis is a serious manifestation of liver diseases with limited therapies. Rhubarb, a widely used herbal medicine, has been frequently used at a relatively large dose for treating cholestasis. However, whether large doses are optimal and the therapeutic mechanism remain unclear. To explore these questions, the anti-cholestatic effect of five doses of rhubarb (0.21, 0.66, 2.10, 6.60, and 21.0 g/kg) in an alpha-naphthylisothiocyanate (ANIT)-induced rat model of cholestasis was examined by histopathology and serum biochemistry. A dose-dependent anti-cholestatic effect of rhubarb (0.21-6.6 g/kg) was observed, and an overdose of 21.0 g/kg showed a poor effect. LC-MS-based untargeted metabolomics together with pathway analysis were further applied to characterize the metabolic alterations induced by the different rhubarb doses. Altogether, 13 biomarkers were identified. The dose-response curve based on nine important biomarkers indicated that doses in the 0.42-6.61 g/kg range (EC20-EC80 range, corresponding to 4.00-62.95 g in the clinic) were effective for cholestasis treatment. The pathway analysis showed that bile acid metabolism and excretion, inflammation and amino acid metabolism were altered by rhubarb in a dose-dependent manner and might be involved in the dose-response relationship and therapeutic mechanism of rhubarb for cholestasis treatment.

[Analysis on characteristic constituents of crude Aconitum carmichaelii in different regions based on UPLC-Q-TOF-MS].

As a representative variety of hypertoxic herbs, aconite has a very high medicinal value but certain security risks. With the advance of urbanization and industrial transfer and upgrading, traditional geo-authentic regions and emerging regions have gradually coexisted. However, there are significant differences in the geographical distribution, ecological environment and growing cycle in these areas, which may cause intraspecific variations in chemical components, and then affect herb quality and clinical efficacy. Furthermore, there was still lack of in-depth study on characteristic constituents of aconite genuineness. In this paper, an UPLC-Q-TOF-MS was used to investigate the chemical ingredients in Jiangyou aconite, Hanzhong aconite, Butuo aconite and Weishan aconite. The results suggested that using unsupervised PCA method, Jiangyou aconite was similar with Hanzhong aconite in chemical ingredients, but significantly different from ones in emerging regions. Using PLS-DA method, seven characteristic constituents were identified, in which Butuo aconite and Weishan aconite had higher contents of mesaconitine and fuziline, while Jiangyou aconite and Hanzhong aconite had higher contents of hypaconitine, neoline, carmichaeline, and songorine. Based on basic toxicity of each ingredient, we can find that hypaconitine and mesaconitine were the key toxicity factors to distinguish Jiangyou aconite, Butuo aconite, and Weishan aconite. The toxicity of geo-authentic Jiangyou aconite was lower than that of Butuo aconite and Weishan aconite. The lower toxicity in geo-authentic Jiangyou aconite was beneficial for ensuring clinical drug safety, which may be one of the important reasons for the formation of genuine aconite. These results provide new reference data to reveal the formation mechanism of genuine aconite from the perspective of plant secondary metabolite diversity.

[Influence of specification on chemical composition of dissolution and hepatocytes toxicity of Polygonum multiflorum].

According to different toxicities of various aqueous extracts of Polygonum multiflorum on hepatocyte, the impacts of chemical composition on the safety of P. multiforum was studied. In this study, 8 main chemical compositions in aqueous extracts of P. multiflorum were determined by the established HPLC method; at the same time, the inhibition ratios of different aqueous extracts of P. multiflorum on L02 cell were determined. Afterwards, the potential compounds related to the toxicity of P. multiforum were tentatively found through a multiple correlation analysis. The results showed that P. multiforum with different chemical compositions exhibited great differences in dissolution. The hepatocyte toxicity of P. multiflorum powder was much greater than P. multiflorum lumps. In addition, three constituents closely related to toxicity of P. multiflorum were found by multiple correlation analysis. The study revealed that chemical composition of P. multiflorum is closely related to the hepatotoxicity, and the hepatotoxicity of P. multiflorum powder is greater than that of other dosage forms. This study indicates that P. multiflorum with different chemical compositions show varying toxicity, which therefore shall be given high attention.

Screening for biomarkers of liver injury induced by Polygonum multiflorum: a targeted metabolomic study.

Heshouwu (HSW), the dry roots of Polygonum multiflorum, a classical traditional Chinese medicine is used as a tonic for a wide range of conditions, particularly those associated with aging. However, it tends to be taken overdose or long term in these years, which has resulted in liver damage reported in many countries. In this study, the indicative roles of nine bile acids (BAs) were evaluated to offer potential biomarkers for HSW induced liver injury. Nine BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), and hyodeoxycholic acid (HDCA) in rat bile and serum were detected by a developed LC-MS method after 42 days treatment. Partial least square-discriminate analysis (PLS-DA) was applied to evaluate the indicative roles of the nine BAs, and metabolism of the nine BAs was summarized. Significant change was observed for the concentrations of nine BAs in treatment groups compared with normal control; In the PLS-DA plots of nine BAs in bile, normal control and raw HSW groups were separately clustered and could be clearly distinguished, GDCA was selected as the distinguished components for raw HSW overdose treatment group. In the PLS-DA plots of nine BAs in serum, the normal control and raw HSW overdose treatment group were separately clustered and could be clearly distinguished, and HDCA was selected as the distinguished components for raw HSW overdose treatment group. The results indicated the perturbation of nine BAs was associated with HSW induced liver injury; GDCA in bile, as well as HDCA in serum could be selected as potential biomarkers for HSW induced liver injury; it also laid the foundation for the further search on the mechanisms of liver injury induced by HSW.

Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway.

BACKGROUND: Paeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. MATERIALS AND METHODS: Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico. RESULTS: Four major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression. CONCLUSION: The potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis.