2.Food-derived bioactive peptides: health benefits, structure‒activity relationships, and translational prospects.
Hongda CHEN ; Jiabei SUN ; Haolie FANG ; Yuanyuan LIN ; Han WU ; Dongqiang LIN ; Zhijian YANG ; Quan ZHOU ; Bingxiang ZHAO ; Tianhua ZHOU ; Jianping WU ; Shanshan LI ; Xiangrui LIU
Journal of Zhejiang University. Science. B 2025;26(11):1037-1058
Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans
;
Peptides/therapeutic use*
;
Structure-Activity Relationship
;
Functional Food
;
Diabetes Mellitus, Type 2/drug therapy*
;
Biological Availability
;
Alzheimer Disease/drug therapy*
;
Inflammatory Bowel Diseases/drug therapy*
;
Hypertension/drug therapy*
;
Liver Diseases/drug therapy*
;
Bioactive Peptides, Dietary
3.Emerging evidence of inter-organ interaction on drug transporters under liver injury.
Ling JIANG ; Ying DENG ; Ruijing MU ; Wenke FENG ; Xiaonan LIU ; Li LIU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):687-699
Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans
;
Liver/drug effects*
;
Animals
;
Chemical and Drug Induced Liver Injury/metabolism*
;
Membrane Transport Proteins/metabolism*
;
Biological Transport
;
Liver Diseases/drug therapy*
;
Pharmaceutical Preparations/metabolism*
4.First-in-class drug oroxylin A tablets for treating hepatic and gastrointestinal disorders: from preclinical development to clinical research.
Chengju LUO ; Xuhong LI ; Yuan GAO ; Junyi YANG ; Weiming FANG ; Libin WEI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):801-814
Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
Humans
;
Flavonoids/pharmacokinetics*
;
Tablets
;
Animals
;
Gastrointestinal Diseases/drug therapy*
;
Liver Diseases/drug therapy*
;
Drug Development
;
Clinical Trials as Topic
;
Scutellaria baicalensis/chemistry*
5.Discovery of bioactive polycyclic polyprenylated acylphloroglucinol from Hypericum patulum that protects against hepatic ischemia/reperfusion injury.
Bo TAO ; Xiangli ZHAO ; Zhengyi SHI ; Jie LI ; Yulin DUAN ; Xiaosheng TAN ; Gang CHEN ; Changxing QI ; Yonghui ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1104-1110
Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control*
;
Animals
;
Hypericum/chemistry*
;
Phloroglucinol/administration & dosage*
;
Mice
;
Humans
;
Male
;
Liver/blood supply*
;
Apoptosis/drug effects*
;
Molecular Structure
;
Protective Agents/pharmacology*
;
Hepatocytes/drug effects*
;
Mice, Inbred C57BL
;
Liver Diseases/drug therapy*
6.Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism.
Jifeng LI ; Haolin GUO ; Ying DONG ; Shuo YUAN ; Xiaotong WEI ; Yuxin ZHANG ; Lu DONG ; Fei WANG ; Ting BAI ; Yong YANG
Chinese Journal of Natural Medicines (English Ed.) 2024;22(1):4-14
Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans
;
Drugs, Chinese Herbal/pharmacology*
;
Liver Diseases/drug therapy*
;
Antioxidants
;
Polysaccharides/therapeutic use*
;
Medicine, Chinese Traditional
7.Electroacupuncture at acupoints of liver meridian for diminished ovarian reserve of liver depression: a randomized controlled trial.
Qiuping LUO ; Zhihong YANG ; Lingmin JIN ; Panbi CHEN ; Yun JIANG ; Qingke LI ; Wei ZHANG ; Xiaofang YANG
Chinese Acupuncture & Moxibustion 2024;44(11):1261-1266
OBJECTIVE:
To observe the therapeutic effect of electroacupuncture at acupoints of liver meridian in patients with diminished ovarian reserve (DOR) of liver depression.
METHODS:
A total of 62 patients with DOR of liver depression were randomly divided into an electroacupuncture group (31 cases, 1 case discontinued) and a western medication group (31 cases, 1 case was eliminated). Electroacupuncture was applied at bilateral Taichong (LR 3), Ligou (LR 5), Ququan (LR 8), Jimai (LR 12) in the electroacupuncture group, with continuous wave, in frequency of 2 Hz and current of 0.5-1.0 mA, 30 min each time, once every other day, 3 times a week. Femoston was taken orally in the western medication group, oral estradiol tablets were taken for the first 14 days, followed by oral estradiol/progesterone complex tablets for the rest 14 days, 1 tablet a day. Both groups were treated for 3 consecutive menstrual cycles. Before and after treatment, the scores of TCM syndrome, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed, serum levels of follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were detected, and antral follicle count (AFC), peak systolic velocity (PSV) and resistance index (RI) of ovarian artery were measured by color Doppler ultrasound in the two groups, and the clinical efficacy was evaluated after treatment.
RESULTS:
After treatment, the scores of primary symptom and secondary symptom, as well as the total scores of TCM syndrome were decreased compared with those before treatment (P<0.01), the scores of SAS and SDS, as well as the serum FSH levels and RI of ovarian artery were decreased compared with those before treatment (P<0.01), while the serum AMH levels, AFC and PSV of ovarian artery were increased compared with those before treatment (P<0.05, P<0.01) in the two groups. After treatment, in the electroacupuncture group, the primary symptom score of TCM syndrome was higher than that in the western medication group (P<0.01), the secondary symptom score of TCM syndrome and the scores of SAS and SDS were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 70.0% (21/30) in the electroacupuncture group and 73.3% (22/30) in the western medication group respectively, there was no significant difference in the total effective rate between the two groups (P>0.05).
CONCLUSION
Electroacupuncture at acupoints of liver meridian can effectively improve the clinical symptoms, anxiety and depression, regulate the serum sex hormone levels, increase AFC and improve ovarian blood supply in DOR patients of liver depression.
Humans
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Female
;
Electroacupuncture
;
Adult
;
Acupuncture Points
;
Meridians
;
Ovarian Reserve
;
Young Adult
;
Liver Diseases/physiopathology*
;
Liver/metabolism*
;
Ovary/physiopathology*
;
Treatment Outcome
;
Depression/therapy*
8.Application of peer-assisted learning based on Mini-CEX combined with DOPS evaluation in the teaching of autoimmune liver diseases.
Yansheng LIU ; Jiangyi ZHU ; Yulong SHANG ; Ying HAN
Chinese Journal of Cellular and Molecular Immunology 2024;40(12):1146-1150
Objective To explore the effects of peer assistance model based on mini-clinical evaluation exercise (Mini-CEX) combined with direct observation of procedural skill (DOPS) in the teaching of autoimmune liver diseases (AILDs). Methods A total of 115 residents receiving training in the Department of Gastroenterology of Xijing Hospital were selected and divided into a control group and an experimental group according to the order in which they came to the department. The control group received traditional teaching mode, while the experimental group underwent peer assistance model based on Mini-CEX combined with DOPS. Results The experimental group showed significantly higher scores in both clinical competence and medical record documentation compared to the control group. In addition, the experimental group reported higher satisfaction levels in terms of self-learning ability, learning interest, communication skills and cooperation ability. The overall satisfaction of the experimental group is higher than that of the control group. Conclusion The use of peer assisted learning mode based on Mini-CEX and DOPS in the AILD teaching could improve the teaching effects.
Humans
;
Autoimmune Diseases/therapy*
;
Liver Diseases/therapy*
;
Male
;
Female
;
Peer Group
;
Clinical Competence
;
Adult
;
Teaching
;
Learning
9.Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma.
Ling QI ; Bo ZHANG ; Yun LIU ; Lan MU ; Qun LI ; Xi WANG ; Jian Ping XU ; Xing Yuan WANG ; Jing HUANG
Chinese Journal of Oncology 2023;45(3):259-264
Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.
Humans
;
Esophageal Squamous Cell Carcinoma/drug therapy*
;
Esophageal Neoplasms/pathology*
;
Prospective Studies
;
Programmed Cell Death 1 Receptor/therapeutic use*
;
Antineoplastic Combined Chemotherapy Protocols/adverse effects*
;
Liver Diseases/etiology*
10.Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma.
Chinese Journal of Hepatology 2023;31(1):35-41
What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.
Child
;
Humans
;
Cholangitis, Sclerosing/diagnosis*
;
Constriction, Pathologic/complications*
;
In Situ Hybridization, Fluorescence
;
Cholangiocarcinoma/therapy*
;
Liver Diseases/complications*
;
Cholestasis
;
Inflammatory Bowel Diseases/therapy*
;
Bile Ducts, Intrahepatic/pathology*
;
Bile Duct Neoplasms/therapy*

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