Amelioration of chronic prostatitis by fractions of Mongolian medicine Hosta plantaginea flowers via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hosta plantaginea (Lam.) Aschers flower is an important Mongolian medicine beneficial in the treatment of chronic prostatitis (CP) in the absence of scientific evidence. AIM OF THE STUDY: The aim of this study was to reveal the therapeutical effects and potential mechanisms of H. plantaginea flowers extract (HP) and its different polarity fractions (HPA∼D) on autoimmune CP (ACP) model rats. MATERIALS AND METHODS: Sprague-Dawley male rats were randomly assigned to 13 groups (n = 6/group). Except the sham group, all rats were injected with a mixture of prostate antigen and complete Freund's adjuvant on days 0, 7, and 21 to establish ACP model rats. Afterwards, ACP model rats were orally gavaged with HP or HPA∼D (1 and 4 g/kg of raw herbal material) or positive drug (Prostat, 200 mg/kg) daily from day 21 to day 50 for 30 days, while the sham and model groups were treated simultaneously with isopyknic of 0.3% sodium carboxymethyl cellulose. Histopathological analysis, biochemical parameters, and protein expression of prostate tissues were investigated. RESULTS: In comparison with the model group, all fraction groups experienced improved CP effects, including restored body weight, reduced prostate gland edema and prostate index, decreased prostatic leukocytes, increased prostatic lecithin bodies, and alleviated histopathological damage to prostate tissue. Furthermore, all fraction groups markedly inhibited the phosphorylated protein of nuclear factor kappa-B p65 (NF-κB p65), NF-κB inhibitor alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) than the model group. CONCLUSION: All fractions of HP exerted significant anti-CP effects by inhibiting NF-κB, MAPKs, JAK-STAT and PI3K-Akt pathways in ACP model rats. These findings provide scientific evidence that H. plantaginea flowers can be used as a pivotal Mongolian medicine in clinical applications for the treatment of CP.

Revealing the Active Constituents and Mechanisms of Semiliquidambar cathayensis Chang Roots against Rheumatoid Arthritis through Network Pharmacology, Molecular Docking, and in Vivo Experiment.

Semiliquidambar cathayensis Chang roots (SC) are traditional Chinese medicine for treating rheumatoid arthritis (RA). However, the effect and potential mechanism of SC remain unclear. This study aims to reveal the anti-RA constituents and mechanisms of SC based on network pharmacology, molecular docking, and adjuvant-induced arthritis (AIA) model rat experiment. In this work, 9 potential active constituents, including kaempferol, quercetin, naringenin, paeoniflorin, catechin, fraxin, gentianin, hesperetin, and ellagic acid 3,3',4-trimethyl ether, in SC crossed 65 target genes of RA. In addition, 28 core targets were enriched in inflammation and others, among which interleukin-17 (IL-17) and tumor necrosis factor (TNF) were the major targets. The binding of bio-constituents with IL-17 and TNF were performed using molecular docking. Rat experiment demonstrated that the extract of SC restored body weight loss, reduced arthritis score and the indices of thymus and spleen, alleviated ankle joint histopathology, decreased the levels of rheumatoid factor (RF), C-reactive protein (CRP), IL-17, TNF-α, IL-1ß, IL-6, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and matrix metalloproteinase-2 (MMP-2), whereas elevated the levels of IL-4 and IL-10. Collectively, it was the first time to comprehensively reveal the anti-RA efficacy and mechanism of SC via suppressing the inflammatory pathway based on network pharmacology, molecular docking, and experimental verification, which provide chemical and pharmacological evidences for the clinical application of SC.

The therapeutic effects of Lagopsis supina (Steph. ex Willd.) Ikonn.-Gal. fractions in trauma-induced blood stasis model rats.

Background: Lagopsis supina (Steph. ex Willd.) Ikonn.-Gal. has been a traditional Chinese medicine (TCM) for the treatment of blood stasis, inflammation, and diuresis. Moreover, Huo Xue Li Shui theory was an important TCM theory that used to treat many ailments. Nevertheless, the scientific connotation of this theory has not been clearly elucidated so far. Aim of the study: The aim of this study was to explore the scientific connotation of Huo Xue Li Shui with promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuretic effects in trauma-induced blood stasis model (TBSM) rats, taking microporous adsorption resin with water (LSB) and 30% ethanol (LSC) elution fractions from L. supina as a classical demonstration. Materials and methods: 48 rats were randomly assigned into six groups (n = 8/group): the control group, the model group, and model groups treatment with LSB or LSC. The biochemical parameters and protein expression were measured using kit method and Western blot assay, respectively. Results: Both LSB and LSC were effective in elevating body weight, food consumption, and water intake in model rats. In PBCRBS efficacy evaluation, LSB and LSC remarkably improved histopathological tissues. On the other hand, LSB and LSC prominently decreased the contents of plasma viscosity, platelet aggregation rate, thrombin time, prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, thromboxane B2, thromboxane B2/6-keto-prostaglandin F1α, urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor-1(PAI-1), PAI-1/tissue-type plasminogen activator (t-PA), and PAI-1/u-PA, while significantly enhanced the contents of antithrombin III, 6-keto-prostaglandin F1α, and t-PA. In parallel, LSB and LSC obviously down-regulated the levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8, and remarkably up-regulated the level of IL-10. In determining diuretic activities, LSB and LSC prominently elevated urinary excretion volume and the level of atriopeptin, and remarkably reduced the levels of angiotensin II, anti-diuretic hormone, aldosterone, aquaporin 1 (AQP1), AQP2, and AQP3. In addition, LSB and LSC clearly suppressed protein expressions of AQP1, AQP2, and AQP3. Finally, LSB and LSC did not caused urinary pH, Na+, and Cl- electrolytes and had minor effects on K+ and Ca2+ concentrations. Conclusions: LSB and LSC exhibited prominent PBCRBS, anti-inflammatory, and diuretic effects in TBSM rats, thereby supported the traditional folk use of L. supina. This study successfully provided an experimental basis for the scientific connotation of Huo Xue Li Shui.