Investigation of Tannins Transformation in Sanguisorbae Radix Over Carbonizing by Stir-Frying.

Carbonizing by stir-frying (CSF) is the most common technology in botanical folk medicines to enhance the convergence, hemostasis, and antidiarrheal effects. Sanguisorbae Radix (SR), a well-known herbal medicine in China, has extensive therapeutic functions, while charred SR is known as an additional product obtained from SR after CSF. In this study, mass spectrometry was used to investigate the effect of charring on tannins transformation of SR. The findings showed that the content level of tannins in SR decreased significantly after carbonizing process, while their three categories, gallotannins, ellagitannins, and procyanidins, had downward trends in general. Moreover, CSF also induced the polyphenol in SR to release relevant monomers from its origins. Significant amount of hydrolyzable tannins were detected by mass spectrometry, including gallotannins and ellagitannins, suggesting that hydrolysis during CSF yielded gallic and ellagic acid and their derivatives, in addition to sugar moieties. Subsequently, gallic and ellagic acid can further polymerize to form sanguisorbic acid dilactone. The amount of proanthocyanidins, the oligomers of catechin, including procyanidin, procyanidin C2, procyanidin B3, and 3-O-galloylprocyanidin B3, decreased to form catechin and its derivatives, which may further degrade to protocatechualdehyde. Quantitative analysis illustrated that the amount of gallic, pyrogallic, and ellagic acid and methyl gallate, the essential effectors in SR, significantly increased after CSF, with increased ratios of 1.36, 4.28, 10.33, and 4.79, respectively. In contrast, the contents of cathechin and epigallocatechin dropped remarkably with increased ratios of 0.04 and 0.02. Tannins exhibit moderate absorption, while their relevant monomers have a higher bioavailability. Therefore, CSF is proved here to be an effective technique to the release of active monomers from the original polyphenol precursor. This study explored the mechanism by which tannins are transformed upon CSF of SR.

KGC3P attenuates ovalbumin-induced airway inflammation through downregulation of p-PTEN in asthmatic mice.

BACKGROUND: The roots of Korean red ginseng (Panax ginseng C.A.Mey.; KGC) have been used as an herbal supplement to enhance vital energy and immune capacity. Salvia plebeia R.Br. has been used to treat inflammatory diseases. PURPOSE: The aim of this study was to examine the anti-asthmatic effects of a mixture of Korean red ginseng and Salvia plebeia R.Br. (KGC3P), its component nepetin, and their modes of action in alleviating ovalbumin (OVA)-induced asthma in mice. METHOD: BALB/c mice were sensitized with OVA then subjected to intratracheal, intraperitoneal, and aerosol challenges. KGC3P and nepetin were administered orally for four weeks. Airway hyperresponsiveness (AHR), OVA-specific IgE levels, and Th2 cytokine- and gene expression levels in bronchoalveolar lavage fluid (BALF) and splenocytes were measured. Histological and immune cell subtype analyses were performed. PTEN and Akt phosphorylation levels were also evaluated. RESULTS: KGC3P reduced OVA-induced AHR, serum IgE levels, histological changes, and eosinophils infiltration but also the absolute number of immune cell subtypes including CD3+/CD4+, CD3+/CD8+, CD4+/CD69+, and Gr-1+/CD11b+ in the lungs, BALF, and mesenteric lymph nodes (MLN). KGC3P also lowered the Th2 cytokines IL-4, IL-5, and IL-13 in the BALF and splenocytes and downregulated the IL-4, IL-13, IL-17, TNF-α, and MUC5AC genes in the lung. KGC3P upregulated the peroxisome proliferator-activated receptor (PPAR)γ gene but downregulated the p-Akt and p-PTEN phosphorylation. Similar results were obtained with nepetin treatment. CONCLUSION: KGC3P and nepetin are anti-asthmatic because they reduce various immune cells such as eosinophils and Th2 cell as well as Th2 cytokines. These mechanisms may be accompanied by the regulation of PPARγ expression and the PTEN pathway. Taken together, our results indicate that KGC3P and nepetin may potentially prevent and treat asthma.

The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways.

BACKGROUND: Hesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice. METHODS: Hairless male mice (6-week-old) were divided into three groups (n = 7): control, UVB-treated vehicle, and UVB-treated hesperidin groups. UVB-irradiated mice from hesperidin group were orally administered 0.1 mL of water containing 100 mg/kg body weight per day hesperidin. RESULTS: The mean length and depth of wrinkles in the UVB-treated hesperidin group significantly improved after the oral administration of hesperidin, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). UVB irradiation of mice induced epidermal barrier dysfunction including an increase in the transepidermal water loss (TEWL); however, hesperidin decreased the TEWL. UVB irradiation increased the expression of MMP-9 and pro-inflammatory cytokines whereas UVB-treated hesperidin group showed reduced expression. These results indicate that hesperidin showed anti-photoaging activity in the UVB-irradiated hairless mice. In conclusion, hesperidin inhibited the UVB-induced increase in skin thickness, wrinkle formation, and collagen fiber loss in male hairless mice. CONCLUSIONS: These results suggest that hesperidin shows potent anti-photoaging activity by regulating MMP-9 expression through the suppression of MAPK-dependent signaling pathways.

Anti-allodynic effects of N-demethylsinomenine, an active metabolite of sinomenine, in a mouse model of postoperative pain.

Sinomenine, a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum, has been reported to have analgesic effects in various pain animal models. N-demethylsinomenine, the N-demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum. This study examined the anti-allodynic effects of N-demethylsinomenine in a mouse model of postoperative pain. A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice. Acute treatment with N-demethylsinomenine (10-40 mg/kg, s.c.) relieved the mechanical allodynia in a dose-dependent manner. Although there was no difference in maximal analgesic effect between N-demethylsinomenine (40 mg/kg, s.c.) and sinomenine (40 mg/kg, s.c.), the onset of action of N-demethylsinomenine was quicker than sinomenine. Repeated treatment with N-demethylsinomenine (10-40 mg/kg/day, s.c.) also dose-dependently exerted sustained antinociception against postoperative allodynia and did not produce analgesic tolerance and carry-over effect. The anti-allodynia induced by N-demethylsinomenine (40 mg/kg, s.c.) was attenuated by bicuculline, a selective γ-aminobutyric acid type A (GABAA) receptor antagonist. In addition, the doses of N-demethylsinomenine used here did not alter the locomotor activity in mice. Our findings demonstrated that N-demethylsinomenine exerts behaviorally-specific anti-allodynia against postoperative allodynia mediated through the GABAA receptors, suggesting it may be a useful novel pharmacotherapy for the control of postoperative pain.

Bacterial ß-(1,3)-glucan prevents DSS-induced IBD by restoring the reduced population of regulatory T cells.

Bacterial ß-(1,3)-glucan has more advantages in terms of cost, yield and efficiency than that derived from mushrooms, plants, yeasts and fungi. We have previously developed a novel and high-yield ß-(1,3)-glucan produced by Agrobacterium sp. R259. This study aimed to elucidate the functional mechanism and therapeutic efficacy of bacterial ß-(1,3)-glucan in dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD).Mice were orally pretreated with bacterial ß-(1,3)-glucan at daily doses of 2.5 or 5mg/kg for 2 weeks. After 6 days of DSS treatment, clinical assessment of IBD severity and expression of pro-inflammatory cytokines were evaluated. In vivo cell proliferation was examined by immunohistochemistry using Ki-67 and ER-TR7 antibodies. The frequency of regulatory T cells (Tregs) was analyzed by flow cytometry. Natural killer (NK) activity and IgA level were evaluated using NK cytotoxicity assay and ELISA.The deterioration of body weight gain, colonic architecture, disease score and histological score was recovered in DSS-induced IBD mice when pretreated with bacterial ß-(1,3)-glucan. The recruitment of macrophages and the gene expression of proinflammatory cytokines, such as IL-1ß, IL-6 and IL-17A/F, were markedly decreased in the colon of ß-(1,3)-glucan-pretreated mice. ß-(1,3)-Glucan induced the recovery of Tregs in terms of their frequency in DSS-induced IBD mice. Intriguingly, ß-(1,3)-glucan reversed the functional defects of NK cells and excessive IgA production in DSS-induced IBD mice.We conclude that bacterial ß-(1,3)-glucan prevented the progression of DSS-induced IBD by recovering the reduction of Tregs, functional defect of NK cells and excessive IgA production.

Honokiol ameliorates cerebral infarction from ischemia-reperfusion injury in rats.

Honokiol, a constituent extracted from Magnolia officinalis, had been shown be an antioxidant and an anti-platelet agent in biological systems with an anti-arrhythmic effect and a myocardial protective effect on ischemia-reperfusion injury. We examined the neuroprotective effect of honokiol in rats subjected to focal cerebral ischemia. Honokiol was administered intravenously either at fifteen minutes before right middle cerebral artery occlusion (pretreatment groups) or when both common carotid arteries clips were removed (treatment groups). The results showed that there was no significant hemodynamic change after intravenous infusion of honokiol at the dosages of 10(-8), 10(-7) and 10(-6) g/kg in both groups. However, honokiol significantly reduced the total volume of infarction at the doses of 10(-7) or 10(-6) g/kg in both pretreatment and treatment groups. This study suggests that honokiol is a potent neuroprotective agent in focal cerebral ischemia. This beneficial effect may be related to its antioxidant effect and anti-platelet aggregation activity.