Effects of estrogen inhibition formula herbal mixture for danazol-induced precocious puberty in female rats: an experimental study with network pharmacology.

BACKGROUND: This study aimed at determining the effect of the herbal mixture estrogen inhibition formula (EIF) and its possible mechanisms by precocious puberty animal models and network pharmacology-based analysis. METHODS: Precocious puberty animal models were established by a single injection of 300 µg danazol, then female rats were administered EIF, vaginal openings were monitored, uterus and pituitary indices were determined. The levels of ALP, E2, LH, and FSH were measured using ELISA kits. Real-time PCR was performed to evaluate the mRNA expression of GnRH, UNC5C, and netrin-1 in hypothalamic tissues. We applied network pharmacological analysis to predict potential targets and pathways of EIF. RESULTS: EIF delayed danazol-induced early vaginal opening. In the onset model, EIF reduced the increased levels of serum ALP, E2, LH, and FSH; as well as mRNA expressions of GnRH, Netrin-1, and UNC5C. Moreover, long-term administration of EIF not only diminished all impaired factors but also had no effect on the normal development of the animals. The gene set enrichment analysis showed that the targets of EIF are mainly associated with the GnRH signaling and ovarian steroidogenesis pathways. CONCLUSION: EIF could be used in preclinical research for the treatment of precocious puberty by the inhibition of HPGA pre-maturation.

Taekwondo training reduces blood catecholamine levels and arterial stiffness in postmenopausal women with stage-2 hypertension: randomized clinical trial.

Objective: Menopause is associated with a progressive impairment of vascular function and muscular strength in women. Accordingly, the purpose of this study was to determine if Taekwondo training could improve blood catecholamine levels, arterial stiffness, blood pressure (BP) and skeletal muscle strength in postmenopausal women with stage-2 hypertension. Methods: 20 postmenopausal women (70 ± 4 years old) with stage-2 hypertension were randomly assigned to a 1) Taekwondo training (TT; n = 10) or 2) Control (CON; n = 10) group. Taekwondo training was performed for 60 minutes/day, 3 days/week for 12-weeks. Results: There were significant (P < 0.05) group by time interactions for resting epinephrine (EP) and norepinephrine (NE) levels, with EP decreasing in the TT group and NE increasing in the CON group. Additionally, brachial-ankle pulse wave velocity, resting heart rate, and BP were significantly decreased, while hand grip and leg strength were significantly increased in the TT group compared to CON group. Conclusion: These results suggest that Taekwondo training can be a novel and beneficial mode of exercise for improving cardiovascular function and muscular strength in this population. Abbreviations: TT: Taekwondo training group; CON: control group; EP: epinephrine; NE: norepinephrine; ANS: autonomic nervous system; SNS: sympathetic nervous system; baPWV: brachial-ankle pulse wave velocity.

Intermittent PTH 1-34 administration improves the marrow microenvironment and endothelium-dependent vasodilation in bone arteries of aged rats.

Inflammation coincides with diminished marrow function, vasodilation of blood vessels, and bone mass. Intermittent parathyroid hormone (PTH) administration independently improves marrow and vascular function, potentially impacting bone accrual. Currently, the influence of marrow and intermittent PTH administration on aged bone blood vessels has not been examined. Vasodilation of the femoral principal nutrient artery (PNA) was assessed in the presence and absence of marrow. Furthermore, we determined the influence of PTH 1-34 on 1) endothelium-dependent vasodilation and signaling pathways [i.e., nitric oxide (NO) and prostacyclin (PGI2)], 2) endothelium-independent vasodilation, 3) cytokine production by marrow cells, and 4) bone microarchitecture and bone static and dynamic properties. Young (4-6 mo) and old (22-24 mo) male Fischer-344 rats were treated with PTH 1-34 or a vehicle for 2 wk. In the absence and presence of marrow, femoral PNAs were given cumulative doses of acetylcholine, with and without the NO and PGI2 blockers, and diethylamine NONOate. Marrow-derived cytokines and bone parameters in the distal femur were assessed. Exposure to marrow diminished endothelium-dependent vasodilation in young rats. Reduced bone volume and NO-mediated vasodilation occurred with old age and were partially reversed with PTH. Additionally, PTH treatment in old rats restored endothelium-dependent vasodilation in the presence of marrow and augmented IL-10, an anti-inflammatory cytokine. Endothelium-independent vasodilation was unaltered, and PTH treatment reduced osteoid surfaces in old rats. In conclusion, the marrow microenvironment reduced vascular function in young rats, and PTH treatment improved the marrow microenvironment and vasodilation with age. NEW & NOTEWORTHY This study investigated the influence of the marrow microenvironment on bone vascular function in young and old rats. An inflamed marrow microenvironment may reduce vasodilator capacity of bone blood vessels, diminishing delivery of blood flow to the skeleton. In young rats, the presence of the marrow reduced vasodilation in the femoral principal nutrient artery (PNA). However, intermittent parathyroid hormone administration (i.e., a treatment for osteoporosis) improved the marrow microenvironment and vasodilator capacity in old PNAs.

Protective effect of tetrahydrocurcumin against cisplatin-induced renal damage: in vitro and in vivo studies.

The adverse effects of anticancer drugs can prompt patients to end their treatment despite the efficacy. Cisplatin is a platinum-based molecule widely used to treat various forms of cancer, but frequent and long-term use of cisplatin is limited due to severe nephrotoxicity. In the present study, we investigated the protective effect and mechanism of tetrahydrocurcumin on cisplatin-induced kidney damage, oxidative stress, and inflammation to evaluate its possible use in renal damage. Cisplatin-induced LLC-PK1 renal cell damage was significantly reduced by tetrahydrocurcumin treatment. Additionally, the protective effect of tetrahydrocurcumin on cisplatin-induced oxidative renal damage was investigated in rats. Tetrahydrocurcumin was orally administered every day at a dose of 80 mg/kg body weight for ten days, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) in 0.9 % saline on day four. The creatinine clearance levels, which were markers of renal dysfunction, in cisplatin-treated rats were recovered nearly back to normal levels after administration of tetrahydrocurcumin. Moreover, tetrahydrocurcumin exhibited protective effects against cisplatin-induced oxidative renal damage in rats by inhibiting cyclooxygenase-2 and caspase-3 activation. These results collectively provide therapeutic evidence that tetrahydrocurcumin ameliorates renal damage by regulating inflammation and apoptosis.

Increase in antioxidant and anticancer effects of ginsenoside Re-lysine mixture by Maillard reaction.

Ginsenosides are the main active components of Panax ginseng. Structural changes in diol type ginsenosides along with generation of Maillard reaction products (MRPs) are strongly associated with increased free radical-scavenging activities. Ginsenoside Re, one of the major triol type ginsenosides of P. ginseng, possesses a hydrophobic four-ring steroid-like structure with hydrophilic sugar moieties at carbons-3 and -20. The aim of the present study was to identify changes in the structure, antioxidant and anticancer effects of ginsenoside Re upon Maillard reaction. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg(2), Rg(6) and F(4) by heat-processing. Free radical-scavenging activity of the ginsenoside Re-lysine mixture increased upon heat processing. This improved free radical-scavenging activity mediated by antioxidant MRPs, which were generated through Maillard reaction of a glucosyl moiety separated from carbon-20 of ginsenoside Re and lysine. The increased anticancer effect of ginsenoside Re-lysine mixture upon heat processing was mainly derived from the generation of less-polar ginsenosides through the regulation of Bcl-2 and Bax, as well as caspase-dependent apoptotic pathway. These results reported here have shed significant new lights on the mechanism of increased antioxidant and anticancer effects of P. ginseng upon heat processing.

Dendrobium moniliforme attenuates high-fat diet-induced renal damage in mice through the regulation of lipid-induced oxidative stress.

Obesity is an important and preventable risk factor for renal disease. The administration of an antioxidant with a lipid-lowering effect is an important therapeutic approach for kidney disease in obese patients. The present study was conducted to examine whether methanolic extract of Dendrobium moniliforme (DM), one of the most famous traditional medicines used in many parts of the world, has an antioxidant effect in vitro and an ameliorative effect on high-fat diet (HFD)-induced alterations such as renal dysfunction and lipid accumulation in vivo. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of DM extract (IC(50) = 29.6 µg/mL) was increased in a dose-dependent manner. The LLC-PK1 kidney cell damage induced by oxidative stress was significantly inhibited by the treatments with DM extract. In the animal study, DM extract (200 mg/kg) was orally administered every day for nine weeks to HFD-fed mice, and its effect was compared with that of metformin. The administration of DM extract decreased the elevated serum glucose, total cholesterol concentration and renal lipid accumulation in HFD-fed mice. It also ameliorated renal dysfunction biomarkers including serum creatinine and renal collagen IV deposition. Taken together, these results provide important evidence that DM extract exhibits a pleiotropic effect on obesity induced parameters and exerted a renoprotective effect in HFD-fed mice.

Increase in antioxidant effect of ginsenoside Re-alanine mixture by Maillard reaction.

Ginsenoside Re, one of the major triol type ginsenosides contained in Panax ginseng, has a hydrophobic four-ring steroid-like structure with hydrophilic sugar moieties at carbon-3 and -20. The aim of the present study was to identify the changes in structure and antioxidant activity of ginsenoside Re by the Maillard reaction, which has not been reported yet. The free radical-scavenging activity of ginsenoside Re-alanine mixture was increased by heat-processing. Ginsenoside Re was gradually changed into Rg(2), Rg(6) and F(4) by heat-processing, and the glucosyl moiety at carbon-20 was separated. The improved-free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant Maillard reaction products (MRPs). Antioxidant MRPs were generated from the reaction of glucose and alanine. Based on the viability results of LLC-PK1 renal epithelial cells, MRPs and less-polar ginsenosides contributed to the combined renoprotective effect against oxidative renal damage. Maillard reaction is importantly involved in the increased antioxidant effect of ginsenoside by heat-processing.

Important role of Maillard reaction in the protective effect of heat-processed ginsenoside Re-serine mixture against cisplatin-induced nephrotoxicity in LLC-PK1 cells.

The aim of the present study was to verify the important role of Maillard reaction in the protective effect of heat-processed ginsenoside Re-serine mixture against oxidative stress-induced nephrotoxicity. The free radical-scavenging activity of ginsenoside Re-serine mixture was increased by heat-processing. Ginsenoside Re was transformed into less-polar ginsenosides such as Rg(2), Rg(6) and F(4) by heat-processing, and the glucose molecule at carbon-20 was separated. The improved-free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant Maillard reaction products (MRPs) from the reaction of glucose with serine. Moreover, MRPs from ginsenoside Re-serine mixture showed protective effect against cisplatin-induced renal epithelial cell damage.

Anti-inflammatory and Immune-regulatory Effects of Subcutaneous Perillae Fructus Extract Injections on OVA-induced Asthma in Mice.

Perillae fructus (perilla seed) is a traditional medicinal herb used to treat bronchial asthma in Oriental medical clinics. ST36 is one of the most widely used acupuncture points, particularly for immune system regulation. Injection of an herbal extract into an acupuncture point (herbal acupuncture) is a therapeutic technique combining both acupuncture and herbal treatment. Perillae fructus extract was injected subcutaneously (Perillae fructus herbal acupuncture; PF-HA) at acupoint ST36 of OVA-induced asthmatic mice. The lung weight, bronchoalveolar fluid (BALF) cell count, the number of CCR3+, CD11b+, CD4+ and CD3e+/CD69+ cells in the lung, and the level of IgE, IL-4, IL-5 and IL-13 in BALF and serum were then measured. RT-PCR was used to measure the mRNA expression of IL-4, IL-5, IL-13 and TNF-α in the lung. Lung sections were analyzed histologically. PF-HA significantly reduced lung weight, the number of inflammatory cells in the lung and BALF, the levels of IgE and Th2 cytokines in BALF and serum, mRNA expression of Th2 cytokines in the lung, and pathological changes in lung tissue. Our results suggest that PF-HA may have an anti-inflammatory and immune-regulatory effect on bronchial allergic asthma by restoring the Th1/Th2 imbalance in the immune system and suppressing eosinophilic inflammation in airways.