Stauntonia hexaphylla leaf extract (YRA-1909) suppresses inflammation by modulating Akt/NF-κB signaling in lipopolysaccharide-activated peritoneal macrophages and rodent models of inflammation.

BACKGROUND: Inflammation is emerging as a key contributor to many vascular diseases and furthermore plays a major role in autoimmune diseases, arthritis, allergic reactions, and cancer. Lipopolysaccharide (LPS), which is a component constituting the outer membrane of Gram-negative bacteria, is commonly used for an inflammatory stimuli to mimic inflammatory diseases. Nuclear factor-kappa B (NF-κB) is a transcription factor and regulates gene expression particularly related to the inflammatory process. Stauntonia hexaphylla (Lardizabalaceae) is widely used as a traditional herbal medicine for rheumatism and osteoporosis and as an analgesic, sedative, and diuretic in Korea, Japan, and China. OBJECTIVE: The purpose of this study was to investigate the anti-inflammatory activity of YRA-1909, the leaf aqueous extract of Stauntonia hexaphylla using LPS-activated rat peritoneal macrophages and rodent inflammation models. RESULTS: YRA-1909 inhibited the LPS-induced nitric oxide (NO) and proinflammatory cytokine production in rat peritoneal macrophages without causing cytotoxicity and reduced inducible NO synthase and prostaglandin E2 levels without affecting the cyclooxygenase-2 expression. YRA-1909 also prevented the LPS-stimulated Akt and NF-κB phosphorylation and reduced the carrageenan-induced hind paw edema, xylene-induced ear edema, acetic acid-induced vascular permeation, and cotton pellet-induced granuloma formation in a dose-dependent manner in mice and rats. CONCLUSIONS: S. hexaphylla leaf extract YRA-1909 had anti-inflammatory activity in vitro and in vivo that involves modulation of Akt/NF-κB signaling. Thus, YRA-1909 is safe and effective for the treatment of inflammation.

Antipostmenopausal effects of Stauntonia hexaphylla and Vaccinium bracteatum fruit combination in estrogen-deficient rats.

BACKGROUND: Climacterium is a series of physical and mental symptoms occurring in women and men due to decreased levels of sex hormones. Women lose the ability to become pregnant due to decreased ovarian estrogen production; the initial symptom being hot flushes. In addition, urogenital atrophy, sexual dysfunction, mood changes, and osteoporosis occur. Extracts of Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) fruits, with a wide range of biological activities, are widely used in traditional herbal medicine. OBJECTIVE: The purpose of this study was to investigate the mitigation of menopausal symptoms, such as hot flushes and postmenopausal osteoporosis after combinatorial treatment with SH and VB (SHVB) of ovariectomized (OVX) rats. DESIGN: We measured the bone regenerative effect of SHVB on receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation in vitro and on ovariectomy-induced osteoporosis in vivo. We investigated the effect of SHVB in a rat model of menopausal hot flushes, in which the tail skin temperature increases following ovariectomy-induced rapid decline in estrogen levels. RESULTS: SHVB inhibited osteoclast formation and tartrate-resistant acid phosphatase activity in primary mouse bone marrow-derived cells. In an estrogen deficiency-induced rat model, measurement of serum bone turnover factors showed that treatment with SHVB lowered the increased bone turnover. Additionally, SHVB decreased OVX-induced bone loss of the total femur. SHVB inhibited osteoclast differentiation, prevented bone mass reduction, and improved trabecular bone structure and biochemical markers in OVX-induced osteoporosis. In addition, administration of SHVB significantly ameliorated the changes in skin temperature in OVX rats. CONCLUSION: SHVB improved the symptoms of menopause. These results provide the foundation for developing SHVB as a natural substance to replace hormones in the future.

Anti-Fatigue Activity of a Mixture of Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. Fruit Extract.

Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. are commonly used in traditional herbal medicine and food and both exhibit antioxidant and anti-inflammatory effects. Herein, hot-water extracts of Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. fruits (1:1 mixture) were used to produce a complex extract NET-1601. The anti-fatigue activity of NET-1601 was evaluated in an in vitro oxidative stress model induced by treating C2C12 myotubes with H2O2. An exhaustive swimming test (EST) in vivo model was established using ICR mice. NET-1601-treated C2C12 myotubes (50, 100, and 200 mg/mL) with H2O2-induced oxidative stress displayed significantly increased cell viability and ATP content, but significantly decreased levels of reactive oxygen species. All NET-1601-treated EST models demonstrated significantly higher maximum swimming rates than control mice. Furthermore, serum lactate, lactate dehydrogenase activity, non-esterified fatty acid, and intramuscular glycogen levels were higher in NET-1601-treated mice than in control mice. In addition, mRNA levels of regulatory factors involved in muscle mitochondrial fatty acid ß-oxidation increased upon NET-1601 treatment. Moreover, catalase, superoxide dismutase, glutathione-S-transferase, and liver glutathione content, and antioxidant activity were higher in NET-1601-treated mice than in control mice. Reduced malondialdehyde levels indicated that NET-1601 treatment inhibited exercise-induced lipid peroxidation. Together, these results suggest that NET-1601 retains antioxidant enzyme activity during oxidative stress, simultaneously enhancing both muscle function via glycogen and fatty acid oxidation, thereby exerting a positive effect on recovery from fatigue.

Cynanchum wilfordii Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Regulating 5α-Reductase and Androgen Receptor Activities in a Rat Model.

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of the prostate gland. Cynanchum wilfordii has been reported to improve sexual behavior in male rats. In this study, we investigated the protective effect of an aqueous extract of C. wilfordii (CWW) against BPH development in a testosterone-induced BPH rat model. The rats were divided into the following six groups: sham/vehicle; BPH/vehicle; BPH/finasteride; and three CWW doses (50, 100, and 200 mg/kg). After a 4-week treatment with CWW, the rats were euthanized at scheduled times, and their prostates were weighed, followed by a histopathological examination. Prostate growth inhibition rates in rats administered CWW 50, 100, and 200 mg/kg were 54.5%, 51.8%, and 50.1%, respectively. The BPH/CWW group showed decreased serum testosterone and dihydrotestosterone (DHT) levels compared to the BPH/vehicle group. Furthermore, the BPH/CWW group showed reduced prostate testosterone and DHT levels compared to the BPH/vehicle group. Mechanistically, the reverse transcription-polymerase chain reaction revealed downregulated mRNA expression levels of the androgen receptor, 5α-reductase, and B-cell lymphoma-2 (Bcl-2) in the BPH/CWW200 group compared with those in the testosterone-induced groups. In conclusion, these findings show the effectiveness of CWW in slowing the progression of testosterone-induced BPH in rats.

Effects of Aqueous Extracts of Cynanchum wilfordii in Rat Models for Postmenopausal Hot Flush.

Menopausal hot flushes (HFs), which manifest as a transient increase in skin temperature, occur most frequently in postmenopausal women, and sometimes negatively influence daily life. We investigated the effect of an aqueous extract of Cynanchum wilfordii (CWW) in a rat model of menopausal HFs, where tail skin temperature (TST) is increased after the rapid estrogen decline induced by ovariectomy. Ten-week-old female rats were ovariectomized and treated with CWW for 1 week. We measured TST and rectal temperatures (RT) and investigated serum estradiol. The TST in ovariectomized (OVX) rats was significantly elevated after ovariectomy compared with control rats, whereas the RT in OVX rats was not elevated. Administration of CWW (200 mg/kg/d for 7 days, p.o.) significantly improved the skin temperature increase in OVX rats. The lower level of serum estradiol in OVX rats was significantly increased by supplying E2, but it was not affected by CWW. The present study indicates a need for future research involving treatment with high concentrations of C. wilfordii and measurement over 24 h.