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Climacteric symptoms, as well as postmenopausal estrogen deficiency, have been associated with many psychological problems and the risk of osteoporosis and heart disease. Therefore, in this study, we aimed to evaluate, for the first time, the dose-dependent effect of water chestnut (WC), also known as Trapa bicornis, a fruit extract, on ovariectomy (OVX)-induced menopause in ICR mice. After bilateral OVX surgery, 200, 100, and 50 mg/kg of WC and 200 mg/kg of pomegranate concentrate powder (PCP) were administered orally for 84 days from 4 weeks after OVX operation. Then, anti-climacteric activities were evaluated in five groups: (1) estrogenic, (2) anti-obesity, (3) hypolipidemic, (4) hepatoprotective, and (5) anti-osteoporosis effects. Different biochemical assays, histopathological and morphological inspections, and mRNA expression findings showed that OVX-induced estrogen deficiency-related AMPK decrease was associated with climacteric symptoms such as obesity, hyperlipidemia, hepatic steatosis, and osteoporosis in ICR mice. However, these climacteric effects were reversed in OVX rats by treating them with WC at a dose relative to the same dose of PCP in OVX-ICR mice (200 and 100 mg/kg). Water chestnut fruit extract demonstrated promise as a complementary treatment for menopausal symptoms, indicating possible uses in the health of women through supplements or prescription drugs.

Osteoarthritis (OA) is a degenerative joint disease that mainly occurs due to the cellular inflammatory response and the destruction of joint cartilage. Natural eggshell membrane (NEM), a byproduct of egg processing, might be a promising knee OA treatment because of its anti-inflammatory properties and resemblance to synovial membrane components. Therefore, we aimed to study the anti-inflammatory effects of NEM in OA, utilizing both in vitro experiments with primary chondrocytes and in vivo studies with a surgical rat model of knee OA. In vitro studies showed that NEM treatment improved cell viability in chondrocytes exposed to interleukin-1α by upregulating chondrogenic genes and inhibiting enzymes that degrade the extracellular matrix (ECM). Furthermore, the anti-inflammatory effects of NEM were observed in chondrocytes induced by lipopolysaccharide. Administering NEM orally for 56 days after OA surgery resulted in enhanced joint swelling reduction and improved mobility in animal models, as well as an increase in bone density and cartilage compressive strength in a concentration-dependent manner. It inhibited inflammatory markers (5-lipoxygenase and prostaglandin E2) and extracellular matrix (ECM)-degrading enzymes (MMP-2 and MMP-9) in both the cartilage and synovium. Simultaneously, there was an upregulation in the expression of chondrogenic genes (Sox9, aggrecan, and Col-2). The histopathological and immunohistochemical analyses demonstrated that NEM’s anti-inflammatory, anti-apoptotic, and chondrogenic properties contributed to the mitigation of joint degradation and synovial inflammation. Therefore, NEM is a potential alternative or functional food agent that addresses both anti-inflammatory and chondroprotective aspects in OA.

Obesity is implicated as a factor in several serious metabolic conditions, including hypertension, cardiovascular disease, and type II diabetes. This study aimed at the development of more potent and safer alternative medications to address these metabolic diseases with minimal side effects. Following oral administration of 400, 200, and 100 of mg/kg fermented Schizandrae fructus pomace extracts (fSFP) once daily for 84 days to high-fat diet (HFD)-supplied ICR mice, respectively, we measured liver enzyme activity related to glucose metabolism, gene expression related to fat metabolism, anti-obesity effect, liver and kidney protection effect, and anti-diabetic effect to confirm the effect of fSFP on improving related complications including obesity and diabetes. In the HFD control group, significant obesity and type II diabetes symptoms were developed. However, oral administration of 200 mg/kg of fSFP showed a protective effect on kidney damage and diabetes complications related to insulin-resistant type II diabetes mellitus, as well as oxidative stress-induced abnormalities in glucose and fat metabolism, comparable to that of metformin 250 mg/kg, a positive control. The major bioactive substance in fSFP was identified as shizandrin, which was quantitated as 1.25 mg/g (w/w). Therefore, fSFP extracts can be taken as a medicinal food in combating obesity and diabetes, two current major health concerns.

The use of natural products in developing respiratory-function-protective pharmaceuticals is actively progressing. However, in this context, the improvement effects of young Asian pear (Pyrus pyrifolia Nakai) extracts have not been evaluated yet. Thus, this study investigated the anti-inflammatory and lung damage improvement effects of immature Asian pear extract (IAP; 400, 200, and 100 mg/kg) using a particulate matter 2.5 μm (PM2.5)-induced sub-acute lung injury mouse model. The experimental results were compared with dexamethasone (0.75 mg/kg), used as a control drug. After two intranasal instillations of PM2.5 and ten doses of IAP extract for eight days, changes in macroscopic lung autopsy, leukocyte fractionation from bronchoalveolar lavage fluid, lung antioxidant defense system, lung histopathology, and mRNA expression in lung tissue were confirmed. Stress-induced inflammatory lung damage through the increased expression of PM2.5-induced PI3K/Akt and p38 MAPK mRNA was significantly suppressed via the administration of IAP extract (400–100 mg/kg). Furthermore, IAP extract administration promoted serous fluid production in lung tissue, increased substance P and ACh levels, and decreased mucus-production-related expression of MUC5AC and MUC5B mRNA. Interestingly, the observed effects showed a dose-dependent manner without serious hepatotoxicity. The results of this study indicate that a proper oral administration of IAP extract could be helpful in protecting against lung diseases, positioning IAP extract as a potential candidate for an alternative agent to safeguard the respiratory system.

Allergic asthma is a chronic inflammatory disease characterized by the infiltration of leukocytes, particularly eosinophils, into the airways, resulting in respiratory dysfunction. To develop new asthma treatment materials with minimal side effects and excellent bioactivities, we evaluated the efficacy of immature Asian pear extract (IAP extract; 400–100 mg/kg) in alleviating ovalbumin (OVA)-induced asthma in female C57BL/6J mice. This study assesses various parameters associated with OVA-induced allergic asthma including lung weight, macroscopic necropsy findings, the total cell count in bronchoalveolar lavage fluid (BALF), the total leukocyte count and leukocyte differential count, serum ovalbumin-specific Ig E (OVA-sIg E) levels, interleukin (IL)-4 and IL-5 contents in BALF, histopathological changes in the lungs, and alterations in oxidative stress and inflammation-related mRNA expressions. The results of this study demonstrate clear asthma-related findings in the OVA control group. However, the oral administration of IAP extract (at doses ranging from 400 to 100 mg/kg) significantly suppressed the anti-inflammatory and antioxidant activities by regulating the expressions of phosphoinositide 3-kinase/protein kinase B/phosphatase and TENsin homolog deleted on chromosome 10 (PI3K/Akt/PTEN), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in a dose-dependent manner. These effects are comparable to those observed with dexamethasone at a concentration of 0.75 mg/kg. As a result, the oral administration of an appropriate dose of IAP extract holds promise as a potential natural drug or health-functional food material for improving respiratory function.

Although the immunomodulatory effects of Astragali Radix extract (AR) have been documented, its anti-mutagenic activity, a problem arising from chemotherapeutic agents, is rarely reported. Therefore, the anti-mutagenic and immunomodulatory effects of AR were investigated using a cyclophosphamide (CPA)-induced immunosuppressed mouse model to develop an alternative immunomodulatory agent. The fluid-bed-dried aqueous extract of AR containing 37.5% dextrin and exopolymers purified from Aureobasidium pullulans SM-2001 (EAP) were used in this study. The therapeutic potentials of AR at doses ranging from 100 mg/kg to 400 mg/kg was estimated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity and splenocyte proliferation assay, body weight and lymphatic organ weight measurements, hematological measurements, serum and spleen cytokine level measurements, natural killer (NK) cell activity measurements, real-time RT-PCR expressions of splenic mRNA, a micronucleus test, histopathological observations, and immunohistochemical measurements. In CPA-treated mice, a clear immunosuppressive effect was observed for all tested parameters. However, the oral administration of AR (100, 200, and 400 mg/kg) showed dose-dependent and favorable inhibitory activities on CPA-induced immunosuppression and mutagenicity as compared to 200 mg/kg EAP. Furthermore, AR (100–400 mg/kg) up-regulated the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) which are related to NK-, T-, and B-cell activation, with no critical cytotoxicity. The results of this study clearly demonstrate that AR at an appropriate oral dose could act as a potential alternative agent with significant anti-mutagenicity and immunomodulatory properties.

Atopic dermatitis (AD) is a chronic and allergic skin disease; however, there is no cure for the disease. Red ginseng is well known to have anti-AD potential, while red ginseng marc (RGM) remaining after ginseng extraction is regarded as useless and discarded. However, it has recently been reported that RGM, particularly fermented RGM (fRGM), still contains bioactive properties. Thus, the anti-allergic effects of fRGM were examined in a 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. Treatments of fRGM alleviated skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion; however, it increased glutathione contents, with downregulated gene expression for inflammatory mediators. Histopathological analyses demonstrated that fRGM suppressed epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved anti-inflammatory, antioxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph nodes. The beneficial effects were observed in the dexamethasone and fRGM groups; however, the antioxidant effects were evident only in the fRGM treatments. These results provide useful information for developing fRGM as a therapeutic source for AD.

Osteoarthritis (OA), the most prevalent articular disease with the clinical syndrome of joint pain accompanied by varying degrees of functional limitation, reduces the quality of elderly life. In this study, the effects of Plebeian sage extract (PS) on anti-inflammatory and anti-articular cartilage degradation activities were evaluated in rats with surgically induced OA. PS supplement for 12 weeks significantly decreased Mankin scores, including inflammatory cell numbers, and improved surface cartilage damage and mean femur and tibia articular cartilage (AC) thicknesses in OA rats. PS diminished IL-1β, IL-6, TNF-α, MMP-2, MMP-3, and MMP-9, as well as lipocalin-2 levels in serum or cartilage, which were increased due to OA. The results suggested that PS decreased joint inflammation and loss of articular cartilage by suppressing provocative responses and synovial tissue decimation in the OA model. Thus, PS may be used as a novel potential therapeutic regime for OA in the elderly.

In this paper, we hypothesized that ShashamKyeongok-go (SKOG) is a mixed preparation of Adenophorae Radix powder (AR) and Kyeongok-go (KOG). SKOG may be served as a novel preventive and/or therapeutic agent for various respiratory diseases. SKOG were orally administered to ICR mice at 400, 200, and 100 mg/kg once a day for 11 days to examine antitussive, expectorant, and anti-inflammatory effects. The NH4OH exposure-induced allergic acute inflammation with coughing responses was dose-dependently and significantly (p < 0.01) inhibited by pretreatment with SKOG at doses of 400, 200, and 100 mg/kg. With these concentrations of SKOG, the thickness of intrapulmonary secondary bronchus mucosa and the number of periodic acid Schiff stain-positive mucous-producing cells were significantly (p < 0.05 or p < 0.01) increased, as a result of the increased amount of phenol red secretion. Subsequently, SKOG showed significant (p < 0.01) anti-inflammatory activities as characterized by reducing the effects of xylene-induced increases of ear weight, thickness of total ear and ear dermis, and number of infiltrated inflammatory cells in the ear dermis, in a dose-dependent manner. These results supported that SKOG might have potential therapeutic effects to be used as an antitussive, expectorant, and anti-inflammatory agents in the prevention or treatment of chronic bronchitis and asthma.

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

An abnormal hair-growth cycle induces hair loss, which affects psychological distress and impairs life quality. Red ginseng marc (RGM) is usually discarded as a byproduct after extracting red ginseng, but several studies have shown that the RGM still has bioactive components including ginsenosides. Therefore, the hair-growth effects of fermented RGM (fRGM) and traditional polyherb formula (PH) were examined in C57BL/6 mice. The dorsal hairs of mice were depilated, and they were topically treated with fRGM or PH at 400, 200 and 100 mg/kg or the combination of both middle doses (combi) once a day for two weeks. The hair-covering regions were significantly increased with higher doses of fRGM and PH and in combi groups, compared with the control treated with distilled water. Hair length, thickness and weight also increased in the treatment groups. In particular, the fRGM and PH increased the anagen-phased hair follicles, the follicular diameters and the dermal thickness. Immunostains for Ki-67 showed the anagen-phased cell division in the treatment groups. The beneficial effects were greater in the high doses of fRGM and PH and the combi groups. These suggest hair-growth-promoting effects of fRGM, PH and the combination by enhancing the hair-growth cycle.

An unripe apple (immature fruit of Malus pumila Mill) contains more polyphenols than mature fruit. To explore the anti-photoaging effects of unripe apple extract (UAE), we investigated the effects of UAE on wrinkle improvement, skin moisturizing, skin inflammation, and antioxidant activities using the ultraviolet B (UVB)-irradiated SKH1-hr hairless mouse model. The mice were irradiated with UVB (0.18 J/cm2) three times per week and orally administrated UAE (100, 200, or 400 mg/kg) once a day for 15 weeks. The administration of UAE significantly prevented UVB-induced wrinkle formation and skin water loss, potentially by increasing the effects of UAE on type I collagen (COL1) and hyaluronic acid through the transcriptional regulation of COL1α (COL1A1 and COL1A2), hyaluronan synthesis (HAS1, HAS2, and HAS3) and the matrix metalloproteinase (MMP1, MMP9, and MMP13) gene. Moreover, UAE significantly reduced UVB-induced skin edema, infiltrated neutrophils, and pro-inflammatory cytokine interleukin-1β (IL-1β), while increasing the anti-inflammatory cytokine IL-10. UAE also exerted anti-oxidative stress properties by increasing the glutathione content and inhibiting lipid peroxidation and superoxide anion production. The histopathological analysis demonstrated that UAE-induced anti-inflammation, anti-oxidative stress, and anti-apoptotic properties on the UVB-irradiated skin tissues. Therefore, UAE may be an effective natural resource to mitigate UVB-induced skin photoaging.

Brassica oleracea var. capitata L. (cabbage) is a popular vegetable with a wide range of pharmacological activities that help to promote human health. The present study investigated the beneficial effects of B. oleracea var. capitata L. extract (BOE) on HCl/ethanol (H/E)-induced gastric damages in mice. Pre-administration of BOE (25–100 mg/kg) for 7 consecutive days significantly decreased macroscopically visible lesion on the gastric mucosa induced by H/E. In addition, results from hematoxylin and eosin-stained gastric tissue showed that BOE inhibited invaded percentage of lesion and prevented the reduction in mucosal thickness in peri-ulcerative region. BOE significantly alleviated the H/E-mediated decreases in Alcian blue binding, total hexose, sialic acid, and collagen in the gastric tissue, suggesting BOE attenuates the gastric damage via preserving the integrity of gastric mucus. Moreover, BOE significantly decreased histamine level in the plasma and reduced mRNA levels associated with secreting gastric acid. Furthermore, BOE inhibited myeloperoxidase activity and suppressed nuclear factor-κB mRNA and its dependent inflammatory genes expression induced by H/E. BOE also strengthened antioxidant enzyme activity, with a mitigating H/E-mediated increase in malondialdehyde level of the gastric tissue. Thus, these results suggest that BOE has the potential to protect the gastric tissue via inhibiting gastric acid secretion, inflammation, and oxidative stress.