Mechanism of Jizhi syrup's prevention and treatment of acute bronchitis based on LPS-iNOS inflammatory mediators' signalling.

ETHNOPHARMACOLOGICAL RELEVANCE: Jizhi syrup (JZTJ) is composed of eight medicinal herbs, including Houttuynia cordata, Fagopyrum dibotrys, Ilex chinensis, Ephedra sinica, Aster tataricus, Peucedanum praeruptorum, Citrus aurantium and Glycyrrhiza uralensis. It is mainly used for coughing caused by exogenous wind heat. Symptoms include fever, aversion to cold, chest and diaphragm tightness, cough and sore throat; and acute bronchitis and acute exacerbation of chronic bronchitis with the above symptoms. PURPOSE: This study aimed to preliminary analyse the chemical components in the liposoluble part of JZTJ, evaluate the anti-inflammatory effect of JZTJ by using six animal and cell models and predict the target and mechanism of acute bronchitis prevention and treatment with JZTJ. METHODS: The chemical components in the liposoluble fraction of JZTJ (extracted by cyclohexane) were quantitatively analysed using gas chromatography-mass spectrometry (GC-MS). Classic non-specific inflammation models and acute bronchitis models were established to systematically evaluate the anti-inflammatory effect of JZTJ. The anti-inflammatory intensity and characteristics of three doses of JZTJ were comprehensively compared on the basis of principal component analysis method at the cellular and overall animal levels. By using lipopolysaccharides (LPSs) as modelling factors, a RAW264.7 macrophage inflammatory response model and a rat acute bronchitis model were created to study the effect of JZTJ on the in-vitro and - vivo LPS-iNOS-inflammatory mediators' inflammatory signalling pathway to reveal the mechanism of acute bronchitis prevention and treatment by JZTJ at the levels of genes, proteins, and inflammatory mediators. RESULTS: Seventeen alkane and ester compounds were preliminarily qualitatively identified from the lipid soluble fraction of JZTJ: dibutyl phthalate, tetradecane, ridecane, n-hexadecanoic acid, pentadecane, n-decanoic acid, 2,6,10,14,18,22-tetracosahexaene, 2,6,10,15,19,23-hexamethyl-(all-E)-; phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-; hexadecane. JZTJ has a significant inhibitory effect on acute non-specific inflammation, specifically inhibiting 'xylene-induced ear swelling in mice', 'acetic acid-induced increased permeability of abdominal capillaries in mice' and 'egg white-induced foot swelling in rats'. The above effects are most evident in high doses, followed by medium doses, whereas low doses have poorer or no effects. JZTJ can prevent and treat acute bronchitis induced by LPS in mice and rats, significantly improve the pathological changes in patchy interstitial and alveolar bleeding with excessive neutrophil infiltration and inhibit the release of inflammatory mediators by LPS-induced RAW264.7 macrophages. Its mechanism of action may be by downregulating the phosphorylation level of p-ERK1/2 protein, thereby inhibiting inducible nitric oxide synthase (iNOS) mRNA, tumour necrosis factor (TNF)-α mRNA and IL-1ß. The expression levels of genes, such as mRNA and IL-6 mRNA, thereby reducing iNOS, TNF-α and IL-1ß. The expression of proteins in the cytoplasm of lung and bronchial tissue cells reduced the release of downstream inflammatory mediators NO and IL-6. CONCLUSION: Preliminary analysis of the chemical components in the lipid soluble fraction of JZTJ can lay the foundation for subsequent research on its effective components. Evaluating the anti-inflammatory effect of JZTJ is helpful for further research on its mechanism of action. The anti-inflammatory effects are exerted by regulating the inflammatory signalling pathway of LPS-iNOS inflammatory mediators, providing a scientific basis for their clinical application.

The application of mirabilite in traditional Chinese medicine and its chemical constituents, processing methods, pharmacology, toxicology and clinical research.

Purpose: This study reviews the use of mirabilite in traditional Chinese medicine and various preparations by describing its chemical composition, processing methods, pharmacology, toxicology, and clinical research progress. Methods: The applications and processing methods of mirabilite are searched in traditional and modern Chinese medical writings, and the articles on chemical composition, pharmacological effects, toxicology, and clinical studies of mirabilite and its combinations in PubMed and China Knowledge Network are reviewed, sorted, and analyzed. Results: The main chemical component of mirabilite is sodium sulfate decahydrate (Na2SO4·10H2O), followed by small amounts of sodium chloride, magnesium sulfate, calcium sulfate, and other inorganic salts. This study systematically organizes the history of the medicinal use of mirabilite in China for more than 2,000 years. This mineral has been used by nine Chinese ethnic groups (Han, Dai, Kazakh, Manchu, Mongolian, Tujia, Wei, Yi, and Tibetan) in a large number of prescription preparations. The Pharmacopoeia of the People's Republic of China (2020 edition) records stated that mirabilite can be used for abdominal distension, abdominal pain, constipation, intestinal carbuncle, external treatment of breast carbuncle, hemorrhoids, and other diseases. The traditional processing methods of mirabilite in China include refining, boiling, sautéing, filtration after hot water blistering, and firing. Since the Ming Dynasty, processing by radish has become the mainstream prepared method of mirabilite. Mirabilite can exhibit anti-inflammatory detumescence effects by inhibiting AMS, LPS, IL-6, IL-10, TNF-α, and NO levels and attenuating the upregulation of TNF-α and NF-κB genes. It can promote cell proliferation and wound healing by increasing the production of cytokines TGFß1 and VEGF-A and gastrointestinal motility by increasing the release of vasoactive intestinal peptide, substance P, and motilin. It can increase the expression of low-density lipoprotein receptor and AKT phosphorylation in the liver by up-regulating bile acid synthesis genes; reduce TRB3 expression in the liver, FGF15 co-receptor KLB expression, and FGF15 production in the ileum, and JNK signal transduction; and increase the transcription of CYP7A1 to achieve a cholesterol-lowering effect. Mirabilite also has a variety of pharmacological effects, such as regulating intestinal flora, anti-muscle paralysis, anti-colon cancer, promoting water discharge, and analgesic. Only a few toxicological studies on mirabilite are available. External application of mirabilite can cause local skin to be flushed or itchy, and its oral administration is toxic to neuromuscular cells. The sulfur ions of its metabolites can also be toxic to the human body. At present, no pharmacokinetic study has been conducted on mirabilite as a single drug. This mineral has been widely used in the clinical treatment of inflammation, edema, wound healing, digestive system diseases, infusion extravasation, hemorrhoids, skin diseases, breast accumulation, muscle paralysis, intestinal preparation before microscopic examination, and other diseases and symptoms. Conclusion: Mirabilite has good application prospects in traditional Chinese medicine and ethnomedicine. In-depth research on its processing methods, active ingredients, quality control, pharmacokinetics, pharmacological and toxicological mechanisms, and standardized clinical application is needed. This paper provides a reference for the application and research of mirabilite in the future.