Antihyperuricemic and Renal Protective Effect of Cordyceps chanhua (Ascomycetes) Fruiting Bodies in Acute Hyperuricemia and Chronic Gout Rodent Models.

Cordyceps chanhua has been widely used in traditional Chinese medicine. The uric acid-lowering effect of artificially cultivated fruiting bodies of C. chanhua (FBCC) was studied using the acute hyperuricemia (AH) and chronic gout (CG) animal models. The AH mice and CG rats were randomly divided into 6 groups: the negative control group, model group, positive control group, low-dose group, medium-dose group, and high-dose group of FBCC, respectively. Serum uric acid, creatinine, urea nitrogen, and liver xanthine oxidase (XOD) activity were detected. Renal tubulointerstitial injury and urate crystals in CG rats were evaluated. The results showed that the uric acid content in AH mice with the high-dose FBCC group decreased statistically (P < 0.05). In the CG rats, the serum uric acid level in all FBCC groups and the serum creatinine value in the high-dose group exhibited a significant decrease (P < 0.05); the scores of renal tubulointerstitial damage and urate deposit were reduced in the high-dose group of FBCC. FBCC can reduce uric acid and improve renal function, demonstrating it as a beneficial supplement for uric acid-lowering and gout-relieving drugs.

Kegan Liyan oral liquid ameliorates lipopolysaccharide-induced acute lung injury through inhibition of TLR4-mediated NF-κB signaling pathway and MMP-9 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Kegan Liyan oral liquid (KGLY), a Chinese prescription modified from classic formulas Yin-Qiao-San (from TCM classic Wenbing Tiaobian) and Shen-Jie-San (first mentioned in Shanghan Wenyi Tiaobian), has been reported to exert heat-clearing and detoxifying effects and used extensively for the treatment of severe pulmonary diseases in clinics including influenza, cough and pneumonia. AIM OF THIS STUDY: The purpose of this study was to investigate the protective effect of KGLY on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with KGLY (50, 100 and 150mg/kg) before intratracheal instillation of LPS. 24h post LPS challenge, lung tissues and the bronchoalveolar lavage fluid (BALF) were collected for lung wet/dry (W/D) weight ratio, histopathological examinations and biochemical analyses. The cell counts, protein concentration, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) in BALF, superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were detected. Meanwhile, the activation of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), as well as matrix metalloproteinases 9 (MMP-9) were determined by western blot assay. RESULTS: KGLY significantly prolonged mice survival time and ameliorated LPS-induced edema, thickening of alveolar septa and inflammatory cell infiltration in a dose-dependent manner. Additionally, KGLY markedly attenuated LPS-induced acute pulmonary inflammation via decreasing the expressions of cytokines and chemokines (IL-1ß, IL-6, TNF-α, and MIP-2), enhanced the activities of anti-oxidative indicators (SOD and GSH), suppressed the levels of MPO and MDA, and down-regulated the expressions of TLR4, NF-κB and MMP9. CONCLUSIONS: The results suggested that the relieving effect of KGLY against LPS-induced ALI might be partially due to suppression of oxidative stress and inflammatory response, inhibition of TLR4-mediated NF-κB activation, and down-regulation of MMP9 expression, indicating it may be a potential therapeutic agent for ALI.

Gastroprotective effect of andrographolide sodium bisulfite against indomethacin-induced gastric ulceration in rats.

Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of andrographolide has been shown to possess anti-inflammatory, antipyretic and analgesic activities. However, there is no report on the gastroprotective effect of ASB against indomethacin-induced gastric ulcer. Here we investigated the possible anti-ulcerogenic potential of ASB and the underlying mechanism against indomethacin-induced gastric ulcer in rats. The ulcer area, histopathological assessment, contents of gastric mucosal glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malonaldehyde (MDA) and prostaglandin E2 (PGE2) were examined. In addition, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) mRNA expression and immunohistochemical evaluation of HSP70, Bcl-2 and Bax proteins were also investigated. Results indicated that ASB pre-treatment significantly reduced the ulcer areas induced by indomethacin compared with the vehicle group. The gastric levels of GSH, CAT and SOD were markedly increased by ASB while the level of MDA was decreased. In addition, ASB pretreatment significantly promoted the gastric PGE2 levels and up-regulated the COX-1 and COX-2 mRNA expression in comparison with the vehicle group. Immunohistochemistry analysis showed obvious up-regulation of HSP70 and Bcl-2 protein expression while suppression of Bax protein in the gastric tissue of ASB-pretreated group. Taken together, these findings indicated that the gastroprotective effect of ASB might be associated with the improvement of antioxidative status, activation of COX-mediated PGE2 synthesis, down-regulation of Bax proteins and up-regulation of Bcl-2 and HSP70 proteins. ASB might have the potential for further development as a promising alternative for antiulcer treatment.

The protective effect of 18ß-Glycyrrhetinic acid against UV irradiation induced photoaging in mice.

It has been confirmed that repeated exposure of skin to ultraviolet (UV) radiation results in cutaneous oxidative stress and inflammation, which act in concert to cause premature skin aging, well known as photoaging. 18ß-Glycyrrhetinic acid (GA), widely used to treat various tissue inflammations, is the main active component of licorice root, and has also been shown to possess favorable anti-oxidative property and modulating immunity function. In the present study, we investigated the potential protective effect of GA on UV-induced skin photoaging in a mouse model. During the experimental period of ten consecutive weeks, the dorsal depilated skin of mice was treated with topical GA for 2 hours prior to UV irradiation. The results showed that GA pretreatment significantly alleviated the macroscopic and histopathological damages in mice skin caused by UV. Meanwhile, the data also indicated that GA markedly up-regulated the activities of the antioxidant enzymes (SOD, GSH-Px), and increased the content of skin collagen, while obviously decreased malonaldehyde level and inhibited high expressions of matrix metalloproteinase-1 (MMP-1) and -3 (MMP-3), as well as down-regulated the expression of inflammatory cytokines such as IL-6, TNF-α and IL-10. Taken together, these findings amply demonstrate that GA observably attenuates UV-induced skin photoaging mainly by virtue of its antioxidative and anti-inflammatory properties, as well as regulating the abnormal expression of MMP-1 and MMP-3.

The protective effects of the supercritical-carbon dioxide fluid extract of Chrysanthemum indicum against lipopolysaccharide-induced acute lung injury in mice via modulating Toll-like receptor 4 signaling pathway.

The supercritical-carbon dioxide fluid extract of Chrysanthemum indicum Linné. (CFE) has been demonstrated to be effective in suppressing inflammation. The aim of this study is to investigate the preventive action and underlying mechanisms of CFE on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results revealed that pretreatment with CFE abated LPS-induced lung histopathologic changes, reduced the wet/dry ratio and proinflammatory cytokines productions (TNF-α, IL-1ß, and IL-6), inhibited inflammatory cells migrations and protein leakages, suppressed the levels of MPO and MDA, and upregulated the abilities of antioxidative enzymes (SOD, CAT, and GPx). Furthermore, the pretreatment with CFE downregulated the activations of NF-κB and the expressions of TLR4/MyD88. These results suggested that CFE exerted potential protective effects against LPS-induced ALI in mice and was a potential therapeutic drug for ALI. Its mechanisms were at least partially associated with the modulations of TLR4 signaling pathways.

Usnic acid protects LPS-induced acute lung injury in mice through attenuating inflammatory responses and oxidative stress.

Usnic acid is a dibenzofuran derivative found in several lichen species, which has been shown to possess several activities, including antiviral, antibiotic, antitumoral, antipyretic, analgesic, antioxidative and anti-inflammatory activities. However, there were few reports on the effects of usnic acid on LPS-induced acute lung injury (ALI). The aim of our study was to explore the effect and possible mechanism of usnic acid on LPS-induced lung injury. In the present study, we found that pretreatment with usnic acid significantly improved survival rate, pulmonary edema. In the meantime, protein content and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) significantly decreased, and the levels of MPO, MDA, and H2O2 in lung tissue were markedly suppressed after treatment with usnic acid. Meanwhile, the activities of SOD and GSH in lung tissue significantly increased after treatment with usnic acid. Additionally, to evaluate the anti-inflammatory activity of usnic acid, the expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and anti-inflammatory cytokine IL-10, and chemokines interleukin-8 (IL-8) and macrophage inflammatory protein-2 (MIP-2) in BALF were studied. The results in the present study indicated that usnic acid attenuated the expression of TNF-α, IL-6, IL-8 and MIP-2. Meanwhile, the improved level of IL-10 in BALF was observed. In conclusion, these data showed that the protective effect of usnic acid on LPS-induced ALI in mice might relate to the suppression of excessive inflammatory responses and oxidative stress in lung tissue. Thus, it was suggested that usnic acid might be a potential therapeutic agent for ALI.

Effects of topical application of patchouli alcohol on the UV-induced skin photoaging in mice.

Ultraviolet (UV) irradiation, known to generate reactive oxygen species (ROS) excessively and elicit inflammatory response, is a potent inducer for skin photoaging. Overproduction of ROS in conjunction with the resulting inflammation stimulate the over-expression of matrix metalloproteinases (MMPs), which in turn causes degradation of extracellular matrix, leading finally to coarse wrinkling, dryness, and laxity of the skin. In this study, patchouli alcohol (PA, C15H26O), an active chemical ingredient reputed for free radical scavenging and anti-inflammatory properties, was investigated for its anti-photoaging action using a mouse model whose dorsal skin was depilated. The dorsal skin areas of six-week-old mice were smeared with PA solution or vehicle, followed by UV irradiation for nine consecutive weeks. Protective effects of PA were evaluated macroscopically and histologically, as well as by assaying the antioxidant enzymes (SOD, GSH-Px) activities, the contents of inflammatory factors (IL-10, IL-6, TNF-α), and the levels of MMP-1 and MMP-3. Our findings amply demonstrated that PA significantly accelerated the recovery of the UV-induced skin lesions, evidently through anti-oxidant and anti-inflammatory action, as well as down-regulation of the MMP-1 and MMP-3 expression.

Prevention of UV radiation-induced cutaneous photoaging in mice by topical administration of patchouli oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin has been widely used in traditional Chinese medicine for the treatment of many diseases, including skin disorders. In the skin beauty and care prescriptions, Pogostemon cablin is one of the top ten frequently used traditional Chinese medicines. AIM OF THE STUDY: The present study was aimed to investigate the protective effects of the essential oil of Pogostemon cablin (patchouli oil, PO) against UV-induced skin photoaging in mice. MATERIALS AND METHODS: To ensure the quality of PO, the chemical compositions of PO were identified, and the content of its chemical marker patchouli alcohol was determined, which was around 28.2% (g/g) in PO. During the experiment period, the dorsal depilated skin of mice was treated with PO for two hours prior to UV irradiation. Then the protective effects of PO on UV-induced skin photoaging were determined by macroscopic and histological evaluations, skin elastic test, collagen content determination and biochemical assays of malondiaidehyde (MDA) content, activities of anti-oxidative indicators including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). RESULTS: Compared to UV exposure groups, present results showed that topical administration of PO, especially at dose of 6mg/mouse and 9mg/mouse, significantly inhibited the increase in skin wrinkle formation, alleviated the reduction in skin elasticity and increased the collagen content by about 21.9% and 26.3%, respectively. We also found that application of 6-9mg/mouse PO could not only decrease the epidermal thickness by about 32.6%, but also prevent the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, the content of MDA was decreased by almost 26.5% and activities of SOD, GSH-Px and CAT were significantly up-regulated after the treatment of PO. CONCLUSION: Results of present study revealed that PO was capable of maintaining skin structural integrity caused by UV irradiation and it was useful in preventing photoaging. These protective effects of PO were possibly due to its anti-oxidative property. Therefore, we suggested that PO should be viewed as a potential therapeutic agent for preventing photoaging.

Inhibitory effect of hydroxysafflor yellow a on mouse skin photoaging induced by ultraviolet irradiation.

Chronic exposure to ultraviolet (UV) irradiation is believed to be the major cause of skin damage that results in premature aging of the skin, so called photoaging, characterized by increases in skin thickness, formation of wrinkles, and loss of skin elasticity. UV induces damage to skin mainly by oxidative stress and collagen degradation. In this study, we examined the photo-protective effect of hydroxysafflor yellow A (HSYA), a major active chemical component isolated from Carthamus tinctorius L., by topical application on the skin of mice. Exposure of the dorsal depilated skin of mice to UV radiation four times a week for 10 weeks induced epidermal hyperplasia, elastin accumulation, collagen degradation, etc. HSYA at the doses of 50, 100, and 200 µg/mouse was topically applied immediately following each UV exposure. The effects of HSYA were evaluated by a series of tests, including macroscopic and histopathological evaluation of skin, pinch test, and redox homeostasis of skin homogenates. Results showed that the UV-induced skin damage was significantly improved after HSYA treatment, especially at doses of 100 and 200 µg/mouse. This protective effect is possibly related to the anti-oxidative property of HSYA and mediated by promoting endogenous collagen synthesis. This is the first study providing preclinical evidence for the protective effect of HSYA against photoaging.