OBJECTIVE: Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis. METHODS: An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels. RESULTS: PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability. CONCLUSION PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure. Please cite this article as: Zhu MJ, Song YJ, Rao PL, Gu WY, Xu Y, Xu HX. Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis. J Integr Med. 2025; 2025; 23(3): 297-308.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Male ; Dysbiosis/drug therapy* ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects* ; Polysaccharides/therapeutic use* ; Prunella/chemistry* ; Mice ; Liver/metabolism* ; Plant Extracts/therapeutic use* ; Disease Models, Animal ; Diet, High-Fat

Traditional Chinese medicine (TCM) plays an important role in preventing and treating diseases and improving human health. However, the complex bioactive components and regulation of signaling pathway and network restrict the elucidation of the mechanisms of action of TCM. A human being is regarded as a super "symbiont" composed of body cells and commensal microorganisms. Gut microbiota is the core commensal microorganism system of a human body, being considered as "the second genome" and the new "organ". Alterations in gut microbiota reflect the state of body health and progression of diseases. Recent investigations have revealed that the TCM rich in polysaccharides and polyphenols can modulate gut microbiota metabolites to rehabilitate gut homeostasis, thus ameliorating diseases via regulating gut-liver axis or gut-brain axis. This review summarizes the causal relationship and mechanisms of action of TCM in the treatment of diseases from the perspective of gut microbiota metabolites. Our findings are expected to provide new insights into the mechanisms of TCM in preventing and treating diseases and guidance for TCM-based drug discovery in the future.
Humans ; Gastrointestinal Microbiome/physiology* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Polyphenols/pharmacology* ; Polysaccharides/pharmacology*

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

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms. The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice, increased colon length, and reduced DAI, spleen index, and pathological damage within the colon. PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity. Meanwhile, PGP restored the levels of Th1, Th2, Th17, and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity. Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation. Taken together, PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.
Animals ; Mice ; Colitis, Ulcerative/drug therapy* ; Platycodon ; Colon/pathology* ; Cytokines ; Anti-Inflammatory Agents/therapeutic use* ; Polysaccharides/therapeutic use* ; Dextran Sulfate ; Disease Models, Animal ; Colitis/chemically induced* ; Mice, Inbred C57BL

Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested. It is fermented by intestinal microflora to promote qualitative and selective changes in the composition of the intestinal microbiome, which often result in beneficial effects on the health of the host. People call it "prebiotics". In this review, we systematically summarized the anti-diabetic effect of traditional Chinese medicine polysaccharides. These polysaccharides regulate the metabolism of sugar and lipids by inter-influence with the intestinal microflora, and maintain human health, while improving type 2 diabetes-like symptoms such as high blood glucose, and abnormal glucose and lipid metabolism.
Blood Glucose/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Humans ; Lipids ; Medicine, Chinese Traditional ; Polysaccharides/pharmacology* ; Probiotics/therapeutic use*

This study aims to explore the molecular mechanism of Lycium barbarum polysaccharides(LBP) in alleviating premature ovarian failure(POF) in mice via the 5'-adenosine monophosphate activated protein kinase(AMPK)/silent information regulator 1(Sirt1) signaling pathway. The POF mouse model was established by D-galactose(D-gal) injection at the back. Six groups were set up, including a normal control group, a model group, a LBP group, a 3-MA(autophagy inhibitor 3-methyladenine) group, an AMPK inhibitor group, and a LBPAMPK inhibitor group, with 15 mice in each group. After 28 continuous days of administration, enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of sex hormones [estradiol(E_2), luteinizing hormone(LH), and follicle-stimulating hormone(FSH)] in serum. The ovarian mass coefficient was measured. Senescence-associated β-Galactosidase(SA-β-Gal) staining and hematoxylin-eosin(HE) staining were performed for observing the state of ovarian senescence and the morphological changes of the ovary. Immunohistochemical method was used to measure the expression of the autophagy marker LC3-Ⅱ in ovarian tissue. Western blot was employed to measure the expression levels of the senescence marker p16~(INK4 a), autophagy markers(LC3-Ⅱ and Beclin-1), the autophagy substrate p62, lysosome-associated membrane protein 2(LAMP2), and the proteins in the AMPK/Sirt1 pathway and mammalian target of rapamycin complex 1(mTORC1)/UNC-51-like kinase 1 Ser757 site(Ulk1 Ser757) pathway. Compared with the normal control group, the modeling of POF decreased the ovarian granulosa cells and follicles, led to the ovarian aging and severe sex hormone secretion disorders, weakened ovarian autophagy activity, and down-regulated the expression of proteins in the AMPK/Sirt1 pathway(P<0.05). Compared with the model group, the treatment with LBP increased ovarian granulosa cells and follicles, alleviated aging and sex hormone disorders, increased autophagy activity, and activated the AMPK/Sirt1 pathway(P<0.05). Both 3-MA and AMPK inhibitor can inhibit autophagy and aggravate ovarian damage and aging in mice. AMPK inhibitor can partially attenuate the role of LBP in promoting autophagy activation and alleviating aging and ovarian tissue damage(P<0.05). LBP can alleviate the symptoms of POF induced by D-gal by promoting the activation of AMPK/Sirt1 pathway.
Animals ; Female ; Humans ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Autophagy/drug effects* ; Follicle Stimulating Hormone/blood* ; Lycium/chemistry* ; Polysaccharides/therapeutic use* ; Primary Ovarian Insufficiency/drug therapy* ; Sirtuin 1/metabolism*

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.
Ammonia/therapeutic use* ; Animals ; Anti-Inflammatory Agents/therapeutic use* ; Cyclooxygenase 2 ; Dendrobium/chemistry* ; Interleukin-17/therapeutic use* ; Interleukin-6 ; NF-kappa B/metabolism* ; Pharyngitis/drug therapy* ; Plant Extracts/chemistry* ; Polysaccharides/pharmacology* ; Rats ; Tumor Necrosis Factor-alpha ; Water

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Cognition ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Monocytes/pathology* ; Polysaccharides/therapeutic use* ; Proteoglycans

In this paper, Asarum polysaccharides(AP) were extracted, and its composition was analyzed to study the activity against H1 N1 influenza virus in vitro and its intervention effect on mice with kidney Yang deficiency syndrome. AP was prepared by the strategy of water extraction and alcohol precipitation, the content was determined, and its monosaccharide composition was analyzed. The cell Real-time monitoring system and Reed-Muench model were adopted to evaluate the antiviral activity of AP in vitro. And the mouse model of kidney Yang deficiency syndrome was established in vivo to compare the efficacy of Mahuang Xixin Fuzi Decoction(MXF) and AP. MXF group and AP group were treated with clinical equivalent doses of 1.8 g·kg~(-1)·d~(-1) and 0.077 g·kg~(-1)·d~(-1) respectively, once a day for 6 consecutive days. Real-time PCR was used to detect the relative expression of M gene of H1 N1 influenza virus and cytokines in lung tissue. The content of AP in Asarum was 25.22%, and the protein content was 0.8%. And the monosaccharide composition was identified as L-rhamnose, D-arabinose, D-xylose, D-glucose, D-galactose and D-mannose. TI values of Tamiflu, MXF and AP were 30.00, 8.06 and 10.33, respectively. Three different doses of AP could significantly reduce the concentration of virus in supernatant. Compared with the model mice, lung indexes of MXF group and AP group decreased significantly(P<0.05), and the relative expression of M gene decreased significantly(P<0.05). The relative expressions of IL-10 and IFN-γ were up-regulated to varying degrees, while the relative gene expressions of IL-1β, IL-6 and MCP-1 were down-regulated to different degrees. In addition, AP could significantly enhance the expression of TNF-α(P<0.01). AP had a good anti-influenza virus activity in vitro, and could protect mice with kidney Yang deficiency syndrome by reducing the viral load in lung tissue, decreasing inflammation damage in lung tissue, and regulating the expression of inflammatory cytokines. Compared with the prescription of MXF, AP had a better antiviral activity.
Animals ; Antiviral Agents/therapeutic use* ; Asarum ; Cytokines/genetics* ; Drugs, Chinese Herbal ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/genetics* ; Lung ; Mice ; Polysaccharides

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; Houttuynia ; chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Inflammation ; drug therapy ; pathology ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Intestinal Mucosa ; drug effects ; metabolism ; microbiology ; pathology ; Lung ; drug effects ; metabolism ; pathology ; Male ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; pathology ; physiopathology ; Plant Extracts ; chemistry ; Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Toll-Like Receptors ; metabolism ; Zonula Occludens-1 Protein ; metabolism