Moslea Herba flavonoids alleviated influenza A virus-induced pulmonary endothelial barrier disruption via suppressing NOX4/NF-κB/MLCK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Moslae Herba, a common traditional Chinese herb with special flavor, has potential for treating respiratory and gastrointestinal diseases. AIM OF THIS STUDY: Lung endothelial barrier dysfunction (LEBD) accelerates the pathogenesis of influenza A virus (IAV)-induced secondary acute lung injury. New strategies against LEBD provide benefits in prevention and treatment of IAV. Previous studies showed that flavonoids (MHF), main bioactivity fraction derived from M. Herba, exerted anti-inflammatory and antiviral activities, but the underlying protection of MHF against IAV-induced acute lung injury remained obscure. The present study was to investigate the protection of MHF against IAV-induced LEBD in vivo and in vitro. MATERIALS AND METHODS: Mice were intranasally challenged with IAV and orally administered with MHF for 5 days. The pulmonary hyperpermeability of infected mice was evaluated by Evans Blue staining and in vivo imaging. Serum levels of inflammatory cytokines and mediators were detected by ELISA assay. The transepithelial electrical resistance (TER) of human pulmonary microvascular endothelial cells (HPMVECs) was measured by using TER meter. The expressions of key proteins in NOX4-mediated NF-κB/MLCK pathways were determined by western blotting. RESULTS: MHF treatment reduced lung index, W/D ratios, and serum levels of inflammatory factors (IL-6, TNF-α, IL-1ß, PLA2, LBT4 and ICAM-1) in IAV-infected mice. Evans blue staining and in vivo imaging results revealed that MHF alleviated IAV-induced barrier dysfunction and pulmonary hyperpermeability. Moreover, luteolin and kaempferol, the main activity compounds in MHF, significantly inhibited TNF-α-induced HPMVEC apoptosis, and downregulated NF-κB/MLCK pathway by targeting NOX4. CONCLUSION: MHF attenuated IAV-induced barrier dysfunction by suppressing NOX4/NF-κB/MLCK pathway and may serve as a potential agent for the prevention of LEBD and IAV.

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common subtype of differentiated thyroid cancers in Asian coastal cities, where the patients have increased risk of potentially high or excessive iodine intake. Given the high metastasis and recurrence of patients with BRAFV600E mutation, the mortality rate of thyroid cancer has recently shown an upward trend. A variety of therapies, including surgery, radiotherapy, and chemotherapy, have been used to treat thyroid cancer, but these therapies still have limitations, including postoperative complications, drug resistance, poor efficacy, or serious side effects. Recent studies have shown the potential of active ingredients derived from herbal medicine in inhibiting PTC via various cell signaling pathways. Some plant-derived compounds, such as apigenin, genistein, and curcumin, are also known to prevent and treat PTC. This article summarizes the recent advances in the structure-functional impact of anti-PTC active ingredients and their effects on PTC cells and tumor microenvironments with an emphasis on their challenges from basic research to clinical practice.

Selaginella uncinata flavonoids ameliorated ovalbumin-induced airway inflammation in a rat model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Selaginella uncinata (Desv.) Spring, known as "Cuiyuncao", is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries. AIM OF THE STUDY: This study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma. MATERIALS AND METHODS: Rats were sensitized and challenged with OVA to induce typical asthmatic reactions. Pathological changes of lung tissue were examined by HE staining. The serum levels of T cell-associated cytokines (IFN-γ, IL-4, IL-5 and IL-13), total IgE and OVA-specific IgE were determined by enzyme-linked immunosorbent assay (ELISA). Gene expressions of T2R10, IP3R1 and Orai1 in lung tissue were assayed by fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) while protein expressions of NFAT1 and c-Myc were assayed by western blot analysis. The activation of SUF was investigated on tansgentic T2R10-GFP HEK293 cells. RESULTS: SUF treatment attenuated airway hyperresponsiveness and goblet cell hyperplasia compared with OVA-challenged asthmatic rats. The serum levels of IL-4, IL-5 and IL-13 as well as total and OVA-specific IgE were decreased while serum IFN-γ was increased in SUF-treated rats. SUF treatment significantly up-regulated T2R10 gene expression, down-regulated IP3R1 and Orai1 gene expression. SUF further suppressed eotaxin, NFAT1 and c-Myc protein expression in lung tissues of OVA-challenged rats. CONCLUSIONS: These results imply that SUF exerts anti-inflammatory function through the T2R10/IP3R1/NFAT1 dependent signaling pathway, and may warrant further evaluation as a possible agent for the treatment of asthma.

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.

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.