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A novel acidic heteropolysaccharide (LCP-90-1) was isolated and purified from a traditional "heat-clearing" Chinese medicine, Lysimachia christinae Hance. LCP-90-1 ( Mw , 20.65 kDa) was composed of Man, Rha, GlcA, Glc, Gal, and Ara, with relative molar ratios of 1.00: 3.00: 11.62: 1.31: 1.64: 5.24. The backbone consisted of 1,4- α -D-Glc p A, 1,4- α -D-Glc p , 1,4- β -L-Rha p , and 1,3,5- α -L-Ara f , with three branches of β -D-Gal p -(1 → 4)- β -L-Rha p -(1→, α -L-Ara f -(1→ and α -D-Man p -(1→ attached to the C-5 position of 1,3,5- α -L-Ara f . LCP-90-1 exhibited potent anticomplement activity (CH 50 : 135.01 ± 0.68 µg/mL) in vitro , which was significantly enhanced with increased glucuronic acid (GlcA) content in its degradation production (LCP-90-1-A, CH 50 : 28.26 ± 0.39 µg/mL). However, both LCP-90-1 and LCP90-1-A were inactivated after reduction or complete acid hydrolysis. These observations indicated the important role of GlcA in LCP-90-1 and associated derivatives with respect to anticomplement activity. Similarly, compared with LCP-90-1, the antioxidant activity of LCP-90-1-A was also enhanced. Thus, polysaccharides with a high content of GlcA might be important and effective substances of L. christinae ., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium, a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg -1 , renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg -1 ·d -1 . The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α-smooth muscle actin (α-SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF-κB) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

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 -1 (d -1 . 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., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The present study aimed to investigate the effects of polysaccharides extracted from Bupleurum chinense DC (BCPs) on macrophage functions. In the in vivo experiment, 1 mL of 5% sodium thioglycollate was injected into the abdomen of the mice on Day 0 and macrophages were harvested on Day 4. The macrophages were cultured in plates and treated with different concentrations of BCPs and stimulus. Effects of BCPs on macrophage functions were assessed by chemotaxis assay, phagocytosis assay and Enzyme-Linked Immunosorbent Assay (ELISA). Our results showed the enhanced chemotaxis, phagocytosis and secretion of nitric oxide (NO) and inflammatory cytokines by macrophages when treated with BCPs. However, when chemotaxis and phagocytosis were up-regulated by complement components or opsonized particles, BCPs inhibited these effects. Also, the NO production induced by lipopolysaccharides (LPS) was suppressed by BCPs mildly. Moreover, BCPs had an inhibitory effect on the [Ca 2+ ] i elevation of macrophages. These results suggested that BCPs exerted modulatory effects on macrophage functions, which may contribute to developing novel approaches to treating inflammatory diseases., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

An Affi-Prep Polymyxin column was combined with a Phenyl Sepharose column and a Sephacryl S-300 column, respectively, to remove the lipopolysaccharides(LPS) in the anti-complementary crude polysaccharides of Houttuynia Herba. The contents of LPS in the polysaccharides were determined by chromogenic tachypleus amebocyte lysate(TAL)method during the procedure of purifying. The anti-complementary activities of the polysaccharides were also compared before and after the removal of LPS. Less remanent LPS was detected after purified using Penyl Sepharose combined with polymyxin column, with the clearance rate of 42.85%. All the columns had no effect on the anti-complementary activity of the polysaccharides. Penyl Sepharose combined with polymyxin column would be sound for LPS removal of the anti-complementary polysaccharides without reducing their bioactivity., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Lipopolysaccharides (LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate (PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages (MPMs). The nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in cell culture supernatant, as the indications of cell response, were assayed. Bupleurum chinensis polysaccharides (BCPs) with trace amount contamination of LPS was treated with PB. 30 μg·mL -1 of PB, treating LPS (10 and 1 000 ng·mL -1 in stimulating RAW264.7 and MPMs respectively) at 37 °C for 24 h, successfully abolished the stimulating effect of LPS on the cells. When the cells were stimulated with LPS, BCPs further promoted NO production. However, pretreated with PB, BCPs showed a suppression of NO production in MPMs and no change in RAW264.7. In the in vitro experiments, LPS contamination in polysaccharide might bring a great interference in assessing the activity of drug. Pretreatment with PB (30 μg·mL -1 ) at 37 °C for 24 h was sufficient to abolish the effects of LPS contamination (10 and 1 000 ng·mL -1 )., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Arnebiaeuchroma (Royle) Johnst (Ruanzicao) is a traditional Chinese herbal medicine (TCM). It is extensively used in China and other countries for treatment of inflammatory diseases. It is known that hyper-activated complement system involves in the fever and acute lung injury (ALI) in rats. In our preliminary studies, anti-complementary activity of crude Arnebiaeuchroma polysaccharides (CAEP) had been demonstrated in vitro. This study aimed to investigate the role and mechanism of crude Arnebiaeuchroma polysaccharides (CAEP) using two animal models, which relate with inappropriate activation of complement system. In lipopolysaccharide (LPS)-induced fever model, the body temperature and leukocytes of peripheral blood in rats were significantly increased, while the complement levels of serum were remarkably decreased. CAEP administration alleviated the LPS-induced fever, reduced the number of leukocytes, and improved the levels of complement. Histological assay showed that there were severe damages and complement depositions in lung of the ALI rats. Further detection displayed that the oxidant stress was enhanced, and total hemolytic activity and C3/C4 levels in serum were decreased significantly in the ALI model group. Remarkably, CAEP not only attenuated the morphological injury, edema, and permeability in the lung but also significantly weakened the oxidant stress in bronchoalveolar lavage fluid (BALF) in the ALI rats. The levels of complement and complement depositions were improved by the CAEP treatment. In conclusion, the CAEP treatment ameliorated febrile response induced by LPS and acute lung injury induced by LPS plus ischemia-reperfusion. CAEP exerted beneficial effects on inflammatory disease potentially via inhibiting the inappropriate activation of complement system.

Mice were immunized with Campylobacter jejuni-S(131) (CJ-S(131)) to establish the lupus-like model. Splenocytes from lupus like mice were challenged with CJ-S(131) to induce inflammatory response in vitro. Bupleurum smithii var. parvifolium polysaccharides (BPs) was added in the inflammatory model to observe its underlying mechanisms of action on lupus. BALB/c mice were randomly divided into three groups including normal control group, adjuvant control group and lupus-like model. Mice were immunized on Day 0 and 14 with CJ-S(131) to establish lupus-like syndrome, and sacrificed on Day 19. Splenocytes from each group were collected and divided into blank control group, BPs added group (BPs 5, 10, 20, 40 μg·m L(-1)), CJ-S(131) stimulated group, and CJ-S(131) plus BPs group. The levels of total IgG, anti-ds DNA antibody, interferon-γ, interleukin-10 (IL-10) and IL-17 were quantified by ELISA. The proliferation of splenocytes was determined in the MTT assay. BPs significantly suppressed the high levels of total IgG, anti-ds DNA antibody, IFN-γ and IL-10 stimulated by CJ-S131 and had no significant effects on increased IL-17 secretion and splenocytes proliferation. The results suggest that re-stimulation of splenocytes with CJ-S(131) could establish an inflammatory model in vitro. The effect of BPs on lupus might is related to its inhibition of the production of autoantibodies and associated cytokines.

Ethnopharmacological Relevance: Houttuynia cordata (HC) has been used as a folk therapy to treat pulmonary infections. This study aimed to determine the role and mechanism of action of polysaccharides isolated from HC (HCP) in lipopolysaccharide (LPS)-induced ALI in the mice., Materials and Methods: LPS was delivered by the intratracheal route to Balb/c mice 2h before HCP (40, 80 and 160mg/kg) administration., Results: The number of total cells, protein and tumor necrosis factor-α (TNF-α) concentrations in bronchoalveolar lavage fluid, the wet/dry weight ratio (w/d) of lungs and pulmonary pathology of each mouse were analyzed, it was found that HCP significantly alleviated ALI induced by LPS. Moreover, in lungs of mice, it was found that the infiltration of inflammatory cells, the expression of Toll-like receptor 4 and complement deposition were significantly decreased by HCP treatment. In vitro assays showed that C5a, a complement activation product, induced significant macrophage migration and treatment with HCP prevented it. The in vitro results also proved that LPS increased nitric oxide and pro-inflammatory cytokines (TNF-α, interleukin-6, and interleukin-1β) production, and HCP antagonized these effects of LPS. It was also found that HCP alone augmented secretion of some pro-inflammatory cytokines., Conclusion: These results indicate that HCP may alleviate LPS induced lung inflammatory injury, which may be associated with its inhibitory effect on the over activation of complement and macrophages. This suggests a potential role to treat ALI., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Bupleurum polysaccharides (BPs), isolated from Bupleurum smithii var. parvifolium, possesses immunomodulatory activity, particularly on inflammation. Bacterial endotoxin lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor 4 (TLR4) on host cell membrane. The present study was performed to evaluate whether the therapeutic efficacy of BPs on suppression of LPS's pathogenecity could be associated with the modulating of TLR4 signaling pathway., Methodology/principal Findings: LPS stimulated expression and activation of factors in the TLR4 signaling system, including TLR4, CD14, IRAK4, TRAF6, NF-κB, and JNK, determined using immunocytochemical and/or Western blot assays. BPs significantly inhibited these effects of LPS. LPS increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12p40, and IFN-β) and NO production, evaluated using ELISA and Griess reaction assays, respectively. BPs antagonized these effects of LPS. Interestingly, BPs alone augmented secretion of some pro-inflammatory cytokines of non-LPS stimulated macrophages and enhanced phagocytic activity towards fluorescent E.coli bioparticles. In a rat model of acute lung injury (ALI) with pulmonary hemorrhage and inflammation, BPs ameliorated lung injuries and suppressed TLR4 expression., Significance: The therapeutic properties of BPs in alleviating inflammatory diseases could be attributed to its inhibitory effect on LPS-mediated TLR4 signaling.

Aim: To isolate and characterize the anti-complementary polysaccharide from the root of Bupleurum chinense., Methods: Bioactivity-guided fractionation and purification was used to obtain the anti-complementary polysaccharide from the hot-water extract of the root of Bupleurum chinense. The polysaccharide was characterized by various chemical and spectral analyses. The anti-complementary activities were evaluated by hemolytic assay in vitro. The action targets were identified in the system with individual complement-depleted sera., Results: A homogeneous polysaccharide BC-PS2 was isolated as an anti-complementary agent. It was identified as a branched polysaccharide with an average molecular weight about 2 000 KDa, composed of Glc, Ara, Gal, and Man in the ratio 3.5 : 2.4 : 2.0 : 1.0, respectively, along with a trace of Rha and Xyl, and only 1.11% of protein. The main linkages of the residues of BC-PS2 include terminal, 1, 6-linked, 1, 3-linked and 1, 3, 6-linked Glcp, terminal and 1, 5-linked Araf, terminal, 1, 4-linked, 1, 6-linked and 1, 4, 6-linked Galp, terminal, and, 1, 4-linked and 1, 4, 6-linked Manp. The bioassay experiments revealed that BC-PS2 inhibited complement activation on both the classical and alternative pathways, with CH50 and AP50 of (0.222 ± 0.013) and (0.356 ± 0.032) mg·mL(-1), respectively. Preliminary mechanism studies indicated that BC-PS2 interacted with C1q, C2, and C9 components., Conclusion: The results demonstrated that BC-PS2 is an anti-complementary polysaccharide, and should be important constituent of the root of Bupleurum chinense for its application in the treatment of diseases associated with the excessive activation of complement system., (Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Radix Bupleuri is a traditional Chinese herb frequently used in the prescriptions for the treatment of inflammatory diseases. This study was to determine whether the crude polysaccharides isolated from the roots of Bupleurum smithii var. parvifolium (BPs) had beneficial effects on a "two-hit" acute lung injury model in rats. A two-hit lung injury model characterized by hemorrhagic shock followed by reperfusion and intratracheal lipopolysaccharide (1 mg kg(-1)) administration was established in Wistar rats. Drugs and saline were administered 30 min after the start of resuscitation. The two-hit acute lung injury model was successfully established. After oral administration, all BPs groups ameliorated pathological injury with lessened complement C3c deposit in lung. BPs 10 and 20 mg kg(-1) diminished the ratio of wet-to-dry weight. In bronchoalveolar lavage (BAL) fluids, the protein concentration, the leukocytes counts, and the lung myeloperoxidase were significantly reduced. BPs also mediated the decreases in interleukin-6 and tumor necrosis factor-α in BAL fluids and in sera. Furthermore, BPs 20 mg kg(-1) decreased the total complement hemolytic activity. BPs had beneficial effects on two-hit acute lung injury. The mechanisms of BPs on inflammatory disease might relate to its inhibitory effect on increased production of proinflammatory mediators and on overactivation of complement.

Bupleurum chinense DC had hepato-protective, anti-inflammatory, antipyretic, analgesic, and immunomodulatory effect in traditional Chinese medicine. This study was to determine whether the crude polysaccharides isolated from the roots of Bupleurum chinense DC (BCPs) attenuated lipopolysaccharide (LPS)-induced acute lung injury in mice. Mice were challenged with LPS intratracheally 2h before BCPs (20, 40 and 80 mg/kg) administration. The bronchoalveolar lavage fluid (BALF) was collected 24h after LPS challenge. Treatment with BCPs reduced lung wet-to-dry weight ratio. The elevated number of total cells and protein concentration in BALF was reduced. The increased level of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) in BALF, and serum nitric oxide (NO) were also inhibited. BCPs significantly attenuated lung injury with improved lung morphology and reduced complement deposition. These results suggested that the effect of BCPs against ALI might be related with its inhibitory effect on excessive activation of complement and on the production of proinflammatory mediators., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease leading to inflammatory tissue damage in multiple organs. The crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium have anticomplementary activity and immunomodulatory functions on macrophages. To study its potential benefit on SLE, we examined effects of BPs on MRL-lpr mice, which have similar disease features to human SLE. MRL-lpr mice were treated orally with BPs 15, 30, or 60 mg kg⁻¹ day⁻¹ for 12 weeks and their SLE characteristics were evaluated. The results revealed that BPs elongated life span, improved kidney function, delayed lymphadenopathy, and reduced autoantibodies. It seemed to be mediated by inhibition of complement and macrophages activation and suppression of interferon-γ (IFN-γ) and interleukin-6 (IL-6) gene expression in the kidney. These results implicate that BPs may be an immunomodulator for the treatment of autoimmune diseases like SLE.

The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional Chinese medicine. This study was to determine whether the crude polysaccharides (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus-like syndrome in mice. BALB/c mice were immunized with CJ-S(131) in Freund's complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg(-1)·day(-1), or prednisone 5 mg kg(-1)·day(-1) was given to BALB/c mice intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg(-1)·day(-1) for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S(131) in BALB/c mice.

Aim of the Study: Radix Bupleuri, one of the most frequently prescribed crude herbs in traditional Chinese medicine, has been used for centuries to treat inflammatory diseases. However, little is known about the therapeutic mechanisms of crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium. Macrophages play important roles in inflammatory diseases such as systemic lupus erythematosus (SLE). The purpose of the present work was to investigate immunomodulative effects of Bupleurum polysaccharides on murine peritoneal macrophages., Materials and Methods: BALB/c mice were administered intragastrically with Bupleurum polysaccharides 20, 40, and 80 mg kg(-1) day(-1), or prednisone 3 mg kg(-1) day(-1) or levamisole 25 mgk g(-1) day(-1) from day 0 to day 6. Peritoneal macrophages were isolated 5 days after intraperitoneal injection of 1 mL 5% sodium thioglycollate. Phagocytic functions of macrophages were studied; cytokines concentrations in the culture supernatants were determined by enzyme-linked immunosorbent assay and the secretion of nitric oxide (NO) was quantified by Griess reaction., Results: Treatment with BPs enhanced phagocytic functions of macrophages (phagocytosis of apoptotic thymocytes, IgG-opsonized sheep red blood cells and chicken red blood cells) and inhibited LPS-induced productions of NO and proinflammatory cytokines (interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha)., Conclusions: Bupleurum polysaccharides up-regulated phagocytic activities but inhibited LPS-induced productions of proinflammatory mediators. These data suggested that at least part of the traditional beneficial effects of Bupleurum on inflammatory diseases could be ascribed to the immunomodulatory effects of Bupleurum polysaccharides on macrophages., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Matteuccia struthiopteris is a nature plant, which contains a lot of potential active components. In the present study, we investigated the effect of polysaccharides extracted from Matteuccia struthiopteris on lupus-like syndrome induced by Campylobacter jejuni CJ-S131 in BALB/c mice. Mice were randomly divided into normal, model control, SLE model (vehicle treated), Matteuccia struthiopteris polysaccharides treated (30 and 15 mg x kg(-1)) groups and prednisone 5 mg x kg(-1) treated groups. The effect of Matteuccia struthiopteris polysaccharides (Ms) on weight and organ index of BALB/c mice was detected. Autoantibodies and total IgG production were measured by enzyme linked immunosorbent assay. Proteinuria was measured and kidneys were examined by light microscopy. Compared with SLE model group, treatment with Matteuccia struthiopteris polysaccharides 30 and 15 mg x kg(-1) reduced weight loss and Matteuccia struthiopteris polysaccharides 15 mg x kg(-1) reduced spleen swelling (P < 0.05). The increased production of autoantibodies and total immunoglobulin G (IgG) were also significantly inhibited. Matteuccia struthiopteris polysaccharides protected kidney against glomerular injury in BALB/c mice with reduced immunoglobulin deposition and lowered proteinuria (P < 0.01). Matteuccia struthiopteris polysaccharides had a protective effect on lupus-like syndrome induced by CJ-S131 in BALB/c mice.

Aim of the Study: Radix Bupleuri, is one of the most frequently prescribed crude herbs in the prescriptions of traditional Chinese medicine for the treatment of inflammatory diseases and auto-immune diseases. This study was to determine whether the crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium, had beneficial effects on autoimmune disease., Materials and Methods: BALB/c mice were immunized with CJ-S(131) in Freund's complete adjuvant on day 0, and then boosted on day 14. BPs 15 or 30 mg kg(-1) day(-1), or prednisone 5 mg kg(-1) day(-1) was given to BALB/c mice intragastrically from day 0 to day 34., Results: Treatment with BPs 15 or 30 mg kg(-1) day(-1) for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. BPs 30 mg kg(-1) day(-1) improved weight loss and spleen swelling when compared with vehicle-treated group., Conclusions: These findings suggested that Bupleurum polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndroma induced by CJ-S(131) in BALB/c mice.

The polysaccharide B3-PS1 was extracted and purified from Herba Scutellariae Barbatae (Scutellaria barbata D. Don), through bioactivity-guided fractionation. Average molecular weight of B3-PS1 was about 1,700,000 Da with a composition of Gal, Glc, Man and Ara in the ratio of 4.3:1.6:1.1:1.0, and trace of Rha, Fuc and Xyl. Preliminary data showed that 1) B3-PS1 inhibited complement activation of the classic pathway with CH(50) value of 0.12 +/- 0.02 mg/ml and of the alternative pathways with AP(50) value of 0.36 +/- 0.05 mg/ml; 2) B3-PS1 interacts with C1q, C1r, C1s, C2, C3, C4, C5 and C9 through a hemolytic assay. These results strongly suggested that B3-PS1 could be a potential candidate in treating those complement-associated diseases such as rheumatoid arthritis, Alzheimer's disease, and Adult Respiratory Distress Syndrome (ARDS).

Our previous study had demonstrated that oral administration of Houttuynia cordata polysaccharides (HCP) without in vitro antiviral activity ameliorated gut and lung injuries induced by influenza A virus (IAV) in mice. However, as macromolecules, HCP was hard to be absorbed in gastrointestinal tract and had no effect on lung injury when administrated intravenously. The action mechanism of HCP was thus proposed as regulating the gut mucosal-associated lymphoid tissue (GALT). Actually, HCP treatment restored the balance of Th17/Treg cells firstly in GALT and finally in the lung. HCP reduced the expression of chemokine CCL20 in the lung and regulated the balance of Th17/Treg carrying CCR6+ (the CCL20 receptor), which was associated with specific migration of Th17/Treg cells from GALT to lung. In vitro , HCP inhibited Th17 cell differentiation through the downregulation of phospho-STAT3, whereas it promoted Treg cell differentiation by upregulating phospho-STAT5. Furthermore, its therapeutic effect was abolished in RORγt−/− or Foxp3−/− mice. These findings indicated that oral administration of macromolecular polysaccharides like HCP might ameliorate lung injury in IAV infected mice via directly regulating the balance of Th17/Treg cells in gut-lung axis. Our results provided a potential mechanism underlying the therapeutic effect of polysaccharides on pulmonary infection. [Display omitted] [ABSTRACT FROM AUTHOR]