A Complex of Cirsium japonicum var. maackii (Maxim.) Matisum. and Thymus vulgaris L. Improves Menopausal Symptoms and Supports Healthy Aging in Women.

We evaluated the efficacy and safety of MS-10® for the treatment of menopausal symptoms. A double-blind randomized placebo-controlled clinical trial was performed in 71 premenopausal women for 4 and 12 weeks. A total of 12 individual menopausal symptom scores were assessed using the Kupperman index. MS-10 treatment effectively improved the symptoms by ∼48%. In addition, the quality of life of the women improved by 36% from four perspectives: vasomotor, psychosocial, physical, and sexual symptoms as evaluated using the menopause-specific quality of life (MenQoL) questionnaire. Our results show that MS-10 improves insulin-like growth factor-1 (IGF-1) and estrogen utilization through receptor activation, which are thought to have causative therapeutic effects on menopause and aging inhibition in women. Improvement of Enthotheline-1 (ET-1) in the blood after MS-10 intake led to an improvement in menopausal vascular symptoms. Improvements in bone formation and absorption markers such as osteocalcin, bone-specific alkaline phosphatase (BSALP), C-telopeptides of type I collagen (CTx), deoxypyridinoline (deoxyPYD), and N-telopeptides of type I collagen (NTx) in blood or urine indicate that MS-10 fundamentally improves bone health in women. By confirming the improvement of the psychological well-being index based on the improvement of stress hormone cortisol, MS-10 can solve causative psychological and physical stress-related symptoms. Moreover, various safety tests, such as those for female hormones, were confirmed. Therefore, it can be confirmed that MS-10 is a natural pharmaconutraceutical that causatively and safely improves health of women and aids in antiaging processes.

YES-10 Improves Stress, Tension, and Fatigue by Reducing Cortisol and IL-6 Levels.

The extract of Clematis mandshurica Rupr. (CMR) inhibits the production of proinflammatory mediators from lipopolysaccharide-stimulated peritoneal macrophages and concanavalin A-stimulated splenocytes. Erigeron annuus Pers. (EAP) extract suppresses the production of reactive oxygen species (ROS) from preadipocytes. Furthermore, the mixture of the leaf extracts of CMR and EAP, YES-10®, protected against nerve injuries induced by ischemia/reperfusion, suggesting a ROS-scavenging action. These observations show the anti-inflammatory action of YES-10. Inflammatory cytokines can cause alterations in mental function, including depression, by influencing the neurotransmitter system. Thus, it was hypothesized that YES-10 could improve mental health, such as depression, anxiety, and sense of well-being. Seventy-two subjects were recruited and randomly divided into YES-10 or placebo groups (n = 36 per group). Each group was daily administered two capsules orally, containing 200 mg of YES-10 or placebo, for 4 weeks in a double-blinded manner and tested for levels of depression, anxiety, well-being, and mental fitness using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychosocial Well-being Index (PWI), and Mental Fitness Scale (MFS). In addition, the levels of cortisol (a stress hormone), interleukin-6 (IL-6) (an inflammatory cytokine), and 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative stress) in the serum were measured. The BDI, BAI, PWI, and MFS scores decreased significantly, and the serum levels of cortisol, IL-6, and 8-OHdG were lowered significantly (P < .05), suggesting that YES-10 has the ability to improve mental health by relieving stress and by decreasing inflammation and oxidative stress.

Anti-Inflammatory Potential of Complex Extracts of Ligularia stenocephala Matsum. & Koidz. and Secale cereale L. Sprout in Chronic Gingivitis: In Vitro Investigation and Randomized Clinical Trial.

Complex extracts of Ligularia stenocephala Matsum. & Koidz. (LSE) and Secale cereale L. sprout (SCSE) (TEES-10®) were prepared. The purposes of the study were to evaluate anti-inflammatory activities of TEES-10® in vitro and to observe resolution of gingivitis in human with oral administration of TEES-10®. The effects of TEES-10® on normal periodontal ligament (PDL) cell viability, lipopolysaccharide (LPS) induced PDL cell viability and the changes of inflammatory mediator expression were evaluated in vitro. In the clinical trial, 150 mg of TEES-10® powder containing capsule was administered twice daily to the test group, while the control group administered placebos in a total 100 participants with gingivitis. Probing depth (PD), bleeding on probing (BOP), clinical attachment loss, gingival index (GI) and plaque index (PI) were measured at baseline and 4 weeks. Administering TEES-10® showed significant increase in PDL cell viability compared to administering LSE or SCSE alone. In addition, treating TEES-10® to LPS induced PDL cell significantly increased PDL cell viability compared to control. TEES-10® suppressed expression of NF-κB, p-ERK, ERK, COX-2, c-Fos and p-STAT and promoted expression of PPARγ in LPS induced PDL cells. In the clinical trial, significant improvement of GI and BOP was observed in the test group at 4 weeks. In addition, the number of patients diagnosed with gingivitis was significantly reduced in the test group at 4 weeks. Salivary MMP-8 and MMP-9 was also significantly decreased compared to placebo group. Within the limitations of this study, the TEES-10® would have an anti-inflammatory potential clinically in the chronic gingivitis patients.

Steroidogenic effects of Taraxacum officinale extract on the levels of steroidogenic enzymes in mouse Leydig cells.

In this study, we investigated the steroidogenic effect of Taraxacum officinale extract on mouse TM3 Leydig cells, which produce male hormones by increasing the levels of steroidogenic enzymes. Steroidogenic enzymes are involved in the production of testosterone in the testis. To date, the steroidogenic effect of T. officinale has not been reported. Therefore, we examined the steroidogenic effects of T. officinale extract (TOE) on mouse Leydig cells in vitro. Traditionally, plants have been used for the treatment of various kinds of ailments. For many years, some medicinal plants have been used to regulate steroidogenesis or late-onset hypogonadism (LOH). In particular, plants belonging to the genus Taraxacum have anti-inflammatory, anti-nociceptive, anti-oxidant, and anti-cancer properties. In this study, we determined whether the TOE exerts steroidogenic effects by increasing the levels of enzymes associated with steroidogenesis, such as the steroidogenic acute regulatory protein (STAR), CYP11A1, and translocator protein (TSPO) in the mitochondria and CYP17A1 in the smooth endoplasmic reticulum, in mouse Leydig cells. Our results showed that the TOE significantly increased the mRNA and protein levels of steroidogenic enzymes, thereby increasing the testosterone levels in mouse Leydig cells. Thus, our results indicate that the TOE increases the levels of steroidogenic enzymes, and further studies are required to establish the potential of this plant in regulating steroidogenesis and improving LOH.

MR-10 Enhances Men's Health by Improving Endogenous Male Sex Hormone Generation.

Although there is a clear need for improving men's health, treatment with suitable natural substances has not yet been well established. Previously, it was reported that MR-10, a novel complex of Korean dandelion and rooibos found by screening many natural products, improved sperm generation and activity. Here, the ability of MR-10 to increase testosterone levels and enhance men's health was tested. Treatment with MR-10 (400 mg/day) for a month significantly increased levels of free testosterone, total testosterone, and the testosterone precursor dehydroepiandrosterone by 22%, 14%, and 32%, respectively, in clinical studies. Also, men's health in terms of mental, physical, and sexual aspects, as determined by using the clinical questionnaires Androgen Deficiency of Aging Men and Aging Males' Symptoms, was improved. Furthermore, the safety of MR-10 was determined by testing levels of prostate-specific antigen, glutamic oxaloacetic transaminase, and glutamic pyruvate transaminase; and the lack of changes due to MR-10 treatment supports the safety of MR-10. In conclusion, this study suggests that MR-10 is a safe and effective natural product improving men's sexual health.

The protective effects of ethanolic extract of Clematis terniflora against corticosterone-induced neuronal damage via the AKT and ERK1/2 pathway.

Chronic stress induces neuronal cell death, which can cause nervous system disorders including Parkinson's disease and Alzheimer's disease. In this study, we evaluated the neuroprotective effects of Clematis terniflora extract (CTE) against corticosterone-induced apoptosis in rat pheochromocytoma (PC12) cells, and also investigated the underlying molecular mechanisms. At concentrations of 300 and 500 µg/ml, CTE significantly decreased apoptotic cell death and mitochondrial damage induced by 200 µM corticosterone. CTE decreased the expression levels of endoplasmic reticulum (ER) stress proteins GRP78, GADD153, and mitochondrial damage-related protein BAD, suggesting that it downregulates ER stress evoked by corticosterone. Furthermore, our results suggested that these protective effects were mediated by the upregulation of p-AKT and p-ERK1/2, which are involved in cell survival signaling. Collectively, our results indicate that CTE can lessen neural damage caused by chronic stress. [BMB Reports 2018; 51(8): 400-405].

Effects of Zanthoxylum piperitum ethanol extract on osteoarthritis inflammation and pain.

Degenerative arthritis, also known as osteoarthritis (OA), is the most common type of arthritis, which is caused by degenerative damage of the cartilage, which primarily protects the joints, leading to inflammation and pain. The objective of this study was to investigate the in vivo and in vitro effects of treatment with ZPE-LR (90% EtOH extract of Zanthoxylum piperitum) on pain severity and inflammation. When using an in vivo OA model MIA (monosodiumidoacetate-induced arthritis) rats, ZPE-LR (100 mg/kg) oral-administratio significantly inhibited MIA-induced change in loaded weight ratio on the left foot, and articular cartilage thickness. To confirm the positive effects on pain relief, acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. Pain related KCNJ6 mRNA expression as well as K + current was increased after ZPE-LR treatment in BV-2 cells. To confirm the positive effects on inflammation, TPA (12-O-tetradecanoylphorbol-13-acetate) induced inflammation measured by mouse ear thickness and biopsy punch weight and TPA-induced iNOS, COX-2 mRNA and protein expression were remarkably suppressed by 50 and 100 mg/kg ZPE-LR oral-administration. In addition, TPA-induced iNOS, COX-2 mRNA level and protein expression were reduced. Acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. We examined in vitro ZPE-LR effects in LPS-induced RAW 264.7 cells. LPS-induced p65 translocation to the nucleus was prohibited by ZPE-LR 100 µg/ml oral administration. Moreover, ROS generation by LPS was significantly inhibited by ZPE-LR 50 and 100 µg/ml treatment. To investigate new ZPE-LR activating mechanisms, the gene fishing method (not a typical term, should probably use PCR based genetic screening) was used. LPS-induced HPRT1 (hypoxanthine phosphoribosyltransferase 1) was decreased by ZPE-LR. However, RPL8 (Ribosomal protein L8) which showed no change in mRNA expression due to LPS, did show increased mRNA levels after ZPE-LR treatment. Our data elucidate mechanisms underlying ZPE-LR and suggest ZPE-LR may be a potential therapeutic agent to modulate osteoarthritis inflammation and pain.

The Natural Substance MS-10 Improves and Prevents Menopausal Symptoms, Including Colpoxerosis, in Clinical Research.

Many natural substances were screened to develop nutraceuticals that reduce menopausal symptoms. A complex of Cirsium japonicum var. maackii and Thymus vulgaris extracts, named MS-10, had significant positive effects. Under a low concentration of estrogen, which represents postmenopausal physiological conditions, MS-10 had beneficial effects on estrogen receptor-expressing MCF-7 cells by reversibly enhancing estrogen activity. In addition, in the ovariectomized rat model, changes in bone-specific alkaline phosphatase activity and osteocalcin, as well as low-density lipoprotein cholesterol and triglyceride levels were significantly decreased by MS-10. These results show that MS-10 protected bone health and reduced metabolic disturbances. Furthermore, in a clinical study, all menopausal symptoms, including hot flushes, parenthesis, insomnia, nervousness, melancholia, vertigo, fatigue, rheumatic pain, palpitations, formication, and headache, as well as colpoxerosis, were significantly improved by taking MS-10 for 90 days. Therefore, the evidence supports that MS-10 is an effective natural substance that can safely improve menopausal symptoms, including colpoxerosis.