Gut microbiota: An emerging therapeutic approach of herbal medicine for prevention of colorectal cancer.

The gut dysbiosis has emerged as a prominent player in the pathogenesis and development of colorectal cancer (CRC), which in turn intensifies dysregulated gut microbiota composition and inflammation. Since most drugs are given orally, this dysbiosis directly and indirectly impinges the absorption and metabolism of drugs in the gastrointestinal tract, and subsequently affects the clinical outcome of patients with CRC. Herbal medicine, including the natural bioactive products, have been used traditionally for centuries and can be considered as novel medicinal sources for anticancer drug discovery. Due to their various structures and pharmacological effects, natural products have been found to improve microbiota composition, repair intestinal barrier and reduce inflammation in human and animal models of CRC. This review summarizes the chemo-preventive effects of extracts and/or compounds derived from natural herbs as the promising antineoplastic agents against CRC, and will provide innovative strategies to counteract dysregulated microbiota and improve the lives of CRC patients.

Polyacetylenes from Codonopsis lanceolata Root Induced Apoptosis of Human Lung Adenocarcinoma Cells and Improved Lung Dysbiosis.

Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in C. lanceolata and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of C. lanceolata polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p-AKT, Bcl-2, cyclin D1, and CDK4 but increased the expression of Bax, GSK-3ß, clv-caspase-3, and clv-caspase-9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in C. lanceolata. CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.

1ß-Hydroxyalantolactone from Inulae Flos alleviated the progression of pulmonary fibrosis via inhibiting JNK/FOXO1/NF-κB pathway.

Inulae Flos was widely distributed throughout Europe, Africa, and Asia, and was commonly used as a folk medicine in clinic for treating various respiratory diseases, including cough, asthma, bronchitis, pulmonary fibrosis, and pneumonia. However, the ingredients responsible for the pharmacology effects of I. Flos and the underlying mechanisms remain unclear. In this study, the effects of 16 known sesquiterpene lactones and flavonoids from I. Flos on TGF-ß1-induced fibroblast activation were assessed by phenotypic high-content screening. Among those sixteen compounds, 1ß-hydroxy alantolactone (HAL), the main characteristic sesquiterpene lactone from I. Flos, exhibited remarkable inhibitory activity. The further studies showed that HAL significantly inhibited the proliferation and induced the apoptosis of human fibroblast cell lines HELF and MRC-5 in a concentration-dependent manner. It also reduced intracellular ROS production, suppressed the mRNA expressions of E-cad, TGF-ß1, Smad3, Col I, α-SMA and TNF-α, and downregulated protein expressions of α-SMA and F-actin. Furthermore, HAL significantly reduced the levels of HA, LN, PC-III and IV-C in serum, TNF-α and IL-6 in BALF, and TGF-ß1, HYP and Col I in lung tissues of bleomycin (BLM)-treated rats. HAL significantly downregulated the expressions of p-JNK, FOXO1, p-p65, α-SMA, p-smad3 and Col I but upregulated p-FOXO1, which could be reversed by JNK agonist anisomycin. These results demonstrated that HAL induced the apoptosis of lung fibroblast cells activated by TGF-ß1 and improved BLM-induced lung fibrosis in rats via inhibiting JNK/FOXO1/NF-κB pathway.

Antihepatofibrotic Effects of Aqueous Extract of Prunella vulgaris on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats.

Prunella vulgaris has been widely used in the folk medicine of Northeastern Asian countries for the treatment of acute liver injury and infectious hepatitis. In the present study, the protective effect of aqueous extract from P. vulgaris was investigated on carbon tetrachloride-induced hepatic fibrosis in vivo. Our data showed that the administration of aqueous extract from P. vulgaris at doses of 50, 100, and 200 mg/kg significantly reduced the elevated serum levels of alanine aminotransferase, aspartate aminotransferase, type III precollagen, and hyaluronic acid in rats with hepatic fibrosis. In addition, aqueous extract from P. vulgaris also reduced the incidence of liver lesions and the formation of fibrous septa, and remarkably decreased the serum levels of inflammatory cytokines, platelet derived growth factor, interleukin-4, interleukin-8, and tumor necrosis factor alpha. Furthermore, aqueous extract from P. vulgaris significantly inhibited the activation of hepatic stellate cells by regulating the expression of α smooth muscle actin, transforming growth factor ß 1, and smad2 and also decreased the deposition of extracellular matrix proteins via regulating the expressions of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase-2,-13. Real-time polymerase chain reaction further revealed that post-treatment with aqueous extract from P. vulgaris decreased the elevated levels of miR-34a and miR-199a-5p in hepatic fibrosis rats. These results demonstrated that aqueous extract from P. vulgaris alleviates carbon tetrachloride-induced hepatic fibrosis by inhibiting the activation of hepatic stellate cells, promoting collagenolysis and regulating fibrosis-related microRNAs.

Hypolipidemic and antioxidant activities of polysaccharides from Rosae Laevigatae Fructus in rats.

Two major fractions (RLP-1 and RLP-2) were obtained by purifying the crude polysaccharides extracted from a traditional Chinese herb Rosae Laevigatae Fructus. The average molecular weight of RLP-1 and RLP-2 was 21.5 kDa and 16.1 kDa, respectively. Monosaccharide analysis indicated that RLP-1 was composed of xylose, mannose and galactose in the molar ratio of 1:11:8, while RLP-2 was only a glucan. Oral administration of RLP-1 could significantly decrease levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), inhibit hepatic lipid accumulation, increase antioxidant lipids and up-regulate expressions of peroxisome proliferator-activated receptor-γ (PPAR-γ) and lipoprotein lipase (LPL) in hyperlipidemia rats. These results suggest that RLP-1 improve hyperlipidemia possibly through regulating PPAR-mediated lipid metabolism. Therefore, could be explored as a possible agent for hyperlipidemia.

Antiviral effects of modified dingchuan decoction against respiratory syncytial virus infection in vitro and in an immunosuppressive mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified dingchuan decoction (MDD) is used in traditional Chinese medicine for the treatment of cough, chronic bronchitis, asthma and viral pneumonia. AIM OF THE STUDY: To investigate antiviral potentials of MDD in respiratory syncytial virus (RSV) infected mice. MATERIALS AND METHODS: MDD and each component were evaluated for antiviral efficacy against RSV in vitro in cell culture. Mice were were treated with cyclophosphamide and infected with RSV. Then, treatments with MDD at doses of 1.75 g/kg, 3.5 g/kg and 7.0 g/kg, respectively, were oral administrated daily for 5 days after challenge. The levels of Eotaxin, IL-4 and IFN-γ in serum and lung tissue were detected by ELISA, viral loads in lung tissues were detected by RFQ-PCR while expressions of NF-κB and TLR4 mRNA were also detected by RFQ-PCR. RESULTS: A selective index of >36.8 (2.5 times greater than that observed for ribavirin) was determined in the in vitro studies for this herbal medicine. MDD exhibited significant antiviral and anti-inflammatory effects on decreasing levels of Eotaxin, IL-4 and IFN-γ in serum and lung tissue, inhibiting pneumonia, decreasing lung viral loads and reversaling RSV-induced inflammation through down-regulation of TLR4 and NF-κB mRNA expression in the lung tissue of RSV-infected mice. CONCLUSIONS: MDD could exhibit antiviral and anti-inflammatory effects on RSV-infected mice as a suppressor of Eotaxin, IL-4 and IFN-γ. These effects appeared to be mediated by inhibitions of TLR4 and NF-κB activation. Therefore, MDD could provide an effective therapeutic approach for RSV and its subsequent viral bronchitis.

Dietary quercetin ameliorates nonalcoholic steatohepatitis induced by a high-fat diet in gerbils.

Dietary quercetin is highly abundant in edible plants, which possesses a wide range of pharmacological properties. This study was to investigate hepatoprotective effects of quercetin in the nonalcoholic steatohepatitis (NASH) gerbils induced by a high-fat diet (HFD), and to evaluate its regulatory mechanism on hepatic inflammatory response. The gerbils were fed with HFD for 28 days to induce NASH. From 15th day to 28th day, the treated drugs were given daily to each animal, respectively. The lipid profiles and biochemical markers were determined at the end of the experiment. The expressions of Sirt1, NF-κB p65 and iNOS were detected by immunohistochemistry and Western blot analysis. The results showed that oral administration of quercetin at doses of 30-60 mg/kg to hyperlipidemia rats for 14 days were highly effective in decreasing the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). It could decrease lipid accumulation in the hepatocytes, and reduce serum levels of pro-inflammatory cytokines TNF-α and IL-6 via regulating the expressions of Sirt1, NF-κB p65 and iNOS. Thus, dietary quercetin had significant therapeutic benefits and could be explored as a potential promising candidate for the prevention of NASH.

Prophylactic effects of Orthosiphon stamineus Benth. extracts on experimental induction of calcium oxalate nephrolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Orthosiphon stamineus (OS) popularly known as "diuretic agent" are traditionally used in folk medicine in the treatment of hyperuricemia, rheumatism, gout, nephritis, nephrolithiasis, urethritis and cystitis. AIM OF THE STUDY: To evaluate prophylactic potentials of total flavonoids, total phenolics and polysaccharides from OS on experimental induction of calcium oxalate (CaOx) nephrolithiasis in rats. MATERIALS AND METHODS: Nephrolithic rats were induced by treating with 1.0% ethylene glycol and 1.0% ammonium chloride for 7 days. Rats in the treated groups were also given OS extracts at the doses of 80 mg/kg and 160 mg/kg. Urine samples (4h) and serum samples were collected at 7th day for biochemical analysis. Kidney tissues were stained with H.E. and analyzed by light microscopy. Expressions of OPN protein were detected by immunohistochemistry. Rates of nucleation and aggregation of calcium oxalate crystals were derived from 20-min time-course measurements of optic density at 620 nm after mixing solutions containing calcium chloride, sodium oxalate and OS extracts at 37°C, pH 5.7. RESULTS: Polysaccharides exhibited the most significant prophylactic effects by reversing BUN and S(cr) levels, ameliorating histopathological changes, increasing urine C(2)O(4)(2-) and Ca(2+) excretion and down-regulating OPN protein expression of kidney in the model rats in comparison with those effects of total flavonoids and total phenolics. Polysaccharides could also significantly inhibit both nucleation and aggregation of CaOx crystals. CONCLUSIONS: Polysaccharides were the main therapeutic materials in OS. It had impressive prophylactic effects on CaOx stones in nephrolithic rats, playing a role as a regulator of OPN protein expression to increase urine C(2)O(4)(2-) and Ca(2+) excretion and also as an inhibitor of CaOx crystallization.

Chemical compositions and anti-influenza activities of essential oils from Mosla dianthera.

ETHNOPHARMACOLOGICAL RELEVANCE: Mosla dianthera as an aromatic herb is used in folk medicine for the treatment of cough, colds, fever, bronchitis, nasal congestion and headache. AIM OF THE STUDY: To characterize chemical compositions and to evaluate the anti-influenza effects of essential oils of M. dianthera (MDEO) in influenza virus A (IVA) infected mice. MATERIALS AND METHODS: MDEO was obtained by hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS). ICR mice were treated with MDEO for 5 consecutive days at doses of 90-360 mg/kg after post-infected. Levels of Serum IL-4 and IFN-γ were assayed by ELISA. Levels of MOD, SOD, TAOC and GSH-Px in lung tissue were determined by colorimetric method. RESULTS: GC-MS analysis revealed the presence of 29 components that account for 97.74% of phenolic sesquiterpenes and aromatic compounds. The major compounds were elemicin (16.51%), thymol (14.77%), ß-caryophyllene (14.49%), iso-elemicin (9.22%), asarone (6.09%) and α-caryophyllene (5.26%). It had significant effects on decreasing lung viral titers, inhibiting pneumonia, reducing levels of serum IFN-γ and IL-4, and enhancing antioxidant activity in the lung tissue of IVA infected mice. CONCLUSIONS: MPE could exhibit therapeutical effects in IVA infected mice as a suppressor of IVA replication and inflammatory mediators and a promoter of antioxidant potentials. Therefore, MDEO could provide a safe and effective therapeutic candidate for treatment of influenza and its subsequent viral pneumonia.

[Experimental study on treating hyperlipidemic fatty liver with Taizhi'an capsule].

OBJECTIVE: To observe the effects of Taizhi'an capsule in treatment of hyperlipidemic fatty liver. METHOD: The model rats were induced by feeding high caloric diet for 8 weeks, then fifty rats were randomly divided into five groups, and each group had ten rats, the Taizhi'an groups (high dose 1 000 mg x kg(-1), middle dose 500 mg x kg(-1), low dose 250 mg x kg(-1)), the Yishanfu group and the model group. Liver index (liver weight/body weight), liver function, blood lipid, liver lipid, the content of MDA and SOD in liver were assayed after therapy, and observe Pathologic changes in rats liver. RESULT: Liver index, blood lipid, liver lipid, liver function increased significantly (P < 0.001) in model rats, and the content of SOD in liver decreased significantly (P < 0.05), Liver histology expressed mild to moderate fat denaturation; After being treated with high and middle dose of Taizhi'an capsule for six weeks, blood lipid, liver function decreased significantly (P < 0.001), and liver lipid decreased significantly (P < 0.001, P <0.05), the content of SOD in liver increased significantly (P < 0.05), meanwhile liver histology was closed to normal. CONCLUSION: Taizhian capsule is effective in the treatment of hyperlipidemic induced fatty liver.