Astragalus membranaceus and Cinnamomum cassia Stimulate the Hair Follicle Differentiation-Related Growth Factor by the Wnt/ß-Catenin Signaling Pathway.

Astragalus membranaceus and Cinnamomum cassia are used as spices and flavorful ingredients, or medicinal herbs with pharmacological effects. In this study, the hair-growth-promoting effects of the YH complex, a newly developed formula consisting of membranaceus and C. cassia, are investigated with the prediction of its molecular mechanism. The target gene of the YH complex was about 74.8% overlapped with the gene set of 'Hair growth' on the GO Biological Process database. The oral administration of the YH complex promoted hair regrowth and increased hair-shaft thickness in depilated hair loss mice. In addition, the anagen/telogen hair follicle ratio was significantly increased by the YH complex. The growth factors affecting the growth of hair follicles were dose-dependently increased by treatment with the YH complex. The Wnt/ß-catenin signaling pathway expressions in skin tissues were apparently increased by the administration of the YH complex. In conclusion, the YH complex consisting of A. membranaceus and C. cassia induced hair follicle differentiation and preserved the growing-anagen phase by increasing growth factors and the Wnt/ß-catenin signaling pathway, leading to the restoration of hair loss. The YH complex can be a remedy for hair loss diseases, such as alopecia areata, androgenetic alopecia, telogen effluvium, and chemotherapy-induced alopecia.

The Slough of Cicadidae Periostracum Ameliorated Lichenification by Inhibiting Interleukin (IL)-22/Janus Kinase (JAK) 1/Signal Transducer and Activator of Transcription (STAT) 3 Pathway in Atopic Dermatitis.

It is known that animal-origin medicine could be one of effective treatment to remedy atopic dermatitis (AD) by controlling the cytokines. Cicadidae Periostracum (CP), the slough of Cryptotympana pustulata, has been frequently used for treating AD and skin affliction in traditional Korean Medicine. This study is aimed at investigating the ameliorating effects of CP on AD and its potential mechanism. The dinitrochlorobenzene sensitized mice were treated with CP for 2 weeks. The various biomarkers and the dermatitis scores presented that CP treatment can induce the visual and biological improvements of AD model. Pruritus, the most serious symptom of AD, which can cause repeated scratching behaviors and finally lead to lichenification, was reduced with CP treatment by regulating the inflammatory reactions. In addition, CP treatment diminished the number of mast cells that are known for causing inflammatory reactions. Moreover, it is proven that CP can decline secretion of interleukin-22, which means CP treatment has anti-inflammatory effects. CP treatment can correct the imbalance of helper T (Th)1 and Th2, downregulating thymic stromal lymphopoietin that leads to decrease of mRNA level of inflammatory cytokines. The crucial role of CP treatment is controlling of the Janus kinase 1/signal transducer and activator of transcription 3 pathway. In addition, CP treatment has the inhibitory effects on kallikrein related peptidase (KLK) 5 and KLK7. Taken together, CP treatment can ameliorate most symptoms and problems caused by AD disease, improving the AD patients' life quality.

An Integrative Study on the Inhibition of Bone Loss via Osteo-F Based on Network Pharmacology, Experimental Verification, and Clinical Trials in Postmenopausal Women.

The inhibition of bone loss remains a challenge for postmenopausal women, considering the fact that only three anabolic treatments for osteoporosis have been approved by the FDA. This study aimed to investigate the osteogenic capacities of Osteo-F, a newly developed herbal formula, upon integrating network analysis and pre-clinical studies into clinical trials. The network pharmacology analysis showed that a potential mechanism of Osteo-F is closely related to osteoblast differentiation. Consistent with the predicted mechanism, Osteo-F treatment significantly enhanced bone matrix formation and mineralization with collagen expression in osteoblasts. Simultaneously, secreted bone-forming molecules were upregulated by Osteo-F. After the administration of Osteo-F to osteoporotic mice, the femoral BMD and osteocalcin in the serum and bone tissues were significantly improved. Subsequently, a randomized, double-blinded, placebo-controlled clinical trial showed that 253 mg of Osteo-F supplementation for 24 weeks resulted in significant improvements in the Z-score and serum osteocalcin levels of postmenopausal women compared to the placebo, thus indicating bone anabolic efficacy. In the current study, the bone anabolic effect of Osteo-F was determined by activating the differentiation and mineralization of osteoblasts through integrating experiments based on network analysis into clinical trials, with synchronized, reliable evidence, demonstrating that Osteo-F is a novel bone anabolic treatment in postmenopausal women.

Effect and mechanism of Magnolia officinalis pharmacopuncture for treating localized fat via network pharmacology and experimental study.

Background: Recently, for various reasons, the need for non-invasive treatment for localized fat has emerged. This study confirmed whether Magnolia officinalis (MO) pharmacopuncture reduces localized fat by promoting lipolysis and inhibiting adipogenesis. Methods: The network was built using genes related to the active compound of MO and the mode of action of MO was predicted by the functional enrichment analysis. Based on the result from network analysis, 100 µL of 2 mg/mL MO pharmacopuncture was injected into the inguinal fat pad for 6 weeks in obese C57BL/6J mice. Normal saline was injected into the right-side inguinal fat pad as a self-control. Results: It was expected that the 'AMP-activated protein kinase (AMPK) signaling pathway' would be affected by the MO Network. MO pharmacopuncture reduced the weight and size of inguinal fat in HFD-induced obese mice. The phosphorylation of AMPK along with the increases of lipases was significantly increased by MO injection. Also, the expression levels of fatty acid synthesize-related mediators were suppressed by MO injection. Conclusion: Our results demonstrated that MO pharmacopuncture promoted the expression of AMPK, which has beneficial effects on activation of lipolysis and inhibition of lipogenesis. Pharmacopuncture of MO can be a non-surgical alternative therapy in the treatment of local fat tissue.

Exploring the Potential Effects and Mechanisms of Asarum sieboldii Radix Essential Oil for Treatment of Asthma.

Asthma, a common chronic pulmonary disorder characterized by airway remodeling, hyperresponsiveness and obstruction, can be aggravated by repeated exposure to particulate matter (PM). The potential effect and mechanisms of Asarum sieboldii Radix essential oil (AEO) against asthma were explored based on network pharmacology. AEO was pre-treated using a nebulizer for 3 weeks and the mice were sensitized to ovalbumin (OVA) and PM10 with the co-treatment of AEO for 4 weeks. In addition, A549 lung epithelial cells were sensitized with PM10 to investigate the underlying mechanisms of AEO regarding the lung-fibrosis-related mediators. The target genes of methyl eugenol, a main compound of AEO, were highly matched by 48% with the gene set of asthma. AEO markedly inhibited the increase in epithelial thickness through the accumulation of goblet cells in the airways. Collagen deposition in the lung tissues of OVA+PM10-challenged asthmatic mice was significantly decreased by AEO. AEO also inhibited the influx of inflammatory cells in the bronchoalveolar lavage fluid, as well as the increases in serum IgE and IgG2a and cytokines in the lung tissues. Furthermore, AEO regulated the expressions of fibrotic mediators, especially POSTN and TGF-ß. In conclusion, we expect that AEO can be one of the effective alternative therapeutics to relieve asthma.

Protective effects of Banhasasim-tang, a herbal medicine, against cold restraint stress-induced gastric ulcers.

Banhasasim-tang (BST), a herbal medicine, has been used for nausea and fever from cold damage. This study aimed to investigate the protective effects of BST in cold restraint stress-induced gastric ulcers. Male Sprague Dawley rats were orally treated with various doses of BST including 0.25, 0.5, 1, 3, 6, 9, 12 and 18g/kg based on the human daily intake dose. After treatment once per day for 3 days, rats were restrained into the cold stress chamber for 12h at 4°C to induce gastric ulcers. Gastric hemorrhagic ulcer area was evaluated and serum adrenocorticotropic hormone (ACTH), corticosterone, epinephrine and dopamine levels were determined. Compared to cold stress-induced gastric ulcer rats, hemorrhage ulcer areas were reduced in BST-treated stomach tissues at all concentrations. Increased serum ACTH, corticosterone and epinephrine levels were significantly decreased by BST treatment in cold stress-induced gastric ulcer rats. Moreover, there were increments of serum dopamine levels in 3 and 6g/kg of BST-treated groups. Taken together, BST positively ameliorated cold restraint stress-induced gastric hemorrhage with decrease in serum stress-related biomarkers such as ACTH, corticosterone, epinephrine and dopamine. The 3-6-fold of human daily intake dose of BST exhibited protective effects as a herbal medicine for gastric ulcers.

Efficacy and mechanism of essential oil from Abies holophylla leaf on airway inflammation in asthma: Network pharmacology and in vivo study.

BACKGROUND: Asthma is one of the most common chronic inflammatory diseases of the airways. Essential oil from Abies holophylla leaf (EOA) has been reported to have anti-inflammatory property. This study aimed to predict the inhibitory effect of EOA against asthma by network analysis and to confirm the underlying mechanism of EOA on airway inflammation. PURPOSE AND STUDY DESIGN: The effects and underlying mechanisms of EOA on asthma were investigated by in silico network pharmacology and an experimental in vivo study. METHODS: To define the effectiveness of EOA on asthma, the network pharmacology was constructed using major components of EOA. EOA (0.0003 and, 0.03 v/v%) was aerosolized by nebulizer 3 times a week for 5 min for 7 weeks. After 3 weeks of treating the mice with EOA, asthma was induced by sensitizing them with ovalbumin (OVA) and PM10. The effects of EOA on the IL-17 related signaling pathway was confirmed using an asthmatic model. RESULTS: The network analysis showed that EOA is highly associated with the IL-17-related signaling pathway. EOA inhibited respiratory epithelium hyperplasia, collagen deposition and goblet cell activation in the lung and trachea tissues. In addition, EOA reduced the number of eosinophils, lymphocytes and macrophages in BALF. Furthermore, in the asthmatic model of mice, we showed that EOA inhibited IL-17-related cytokines, increased Treg-related cytokines and decreased the TRAF6 and MAPK and, suppressed the nuclear transcriptional activities of NF-kB. CONCLUSIONS: The network pharmacology and in vivo study indicated that EOA may have an inhibitory effect on airway inflammation in asthma exposure through the IL-17-related signaling pathway.

Promotion of osteogenesis by Sweroside via BMP2-involved signaling in postmenopausal osteoporosis.

Phlomis umbrosa has been traditionally used for bone diseases in traditional Korean Medicine. Sweroside (SOS), marker compounds of P. umbrosa, has been known to promote osteoblast differentiation. In this study, ameliorative effects of SOS on osteoporosis and potential target pathway were investigated. Ovariectomized mice were administered three doses of SOS three times a week for 4 weeks after inducing osteoporosis. Bone mineral content (BMC) and bone mineral density (BMD) were analyzed by dual energy X-ray absorptiometry. A human osteosarcoma cell line (SaOS-2) was differentiated to clarify the promoting effects of SOS on osteoblast differentiation and bone formation. Osteoblastic bone-forming markers were evaluated in lumbar vertebrae (LV) and mineralized SaOS-2 cells. SOS markedly elevated BMC and BMD levels and attenuated the bone marrow adipocytes in the femoral shaft. SOS increased the formation of bone matrix in SaOS-2 cells. Bone morphogenetic protein-2 (BMP2) and runt-related transcription factor 2 (CBFA1) in LV and SaOS-2 cells were up-regulated by SOS. SOS increased alkaline phosphatase (ALPL), osteopontin (SPP1), and bone sialoprotein-1 (BSPH1). In conclusion, SOS induced the formation of mineralized bone matrix by regulating BMP2/CBFA1-mediated molecules. Therefore, SOS could be a therapeutic compound of treatment for osteoporosis by producing the new bone matrix.

LIPOSA pharmacopuncture, a new herbal formula, affects localized adiposity by regulating lipid metabolism in vivo.

Localized adiposity is a serious aesthetic problem and a well-known health risk factor. There is a growing interest in minimally invasive treatment options for excessive fat accumulation, such as pharmacopuncture. LIPOSA is a newly developed pharmacopuncture formula from three natural herbs: The tuber of Pinellia ternata (Thunb.) Breitenb., the whole plant of Taraxacum platycarpum Dahlst. and the root of Astragalus membranaceus Bunge. The present study investigated the effects of pharmacopuncture treatment with LIPOSA on localized adiposity. Male C57BL/6J mice were fed high fat diet for 8 weeks to induce obesity. Then, 100 µl LIPOSA was injected into the left-side inguinal fat pad at various concentrations, including 13.35, 26.7 and 53.4 mg/ml. Normal saline was injected into the right-side inguinal fat pad of each mouse as a control. The treatment was performed three times per week for 2 weeks. The weight and histological changes were analyzed in the inguinal fat pad of the obese mice. The expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), autophagy-related gene (ATG)5, ATG7 and LC3-II, as lipophagy-related factors, were evaluated to confirm the lipid-catabolic effects of LIPOSA. LIPOSA pharmacopuncture markedly decreased the weight of the fat tissue and the size of the adipocytes in the inguinal region of the mouse models of obesity in a dose-dependent manner. The expression levels of ATGL, HSL, ATG5, ATG7 and LC3-II were significantly increased by the LIPOSA treatments. In addition, LIPOSA pharmacopuncture was found to decrease the expression levels of ACC, PPAR-γ and PEPCK. The results indicated that subcutaneous injection of LIPOSA can degrade local fat and induce lipophagic and lipase activation effects. In addition, lipid metabolism related to fat accumulation was regulated by the LIPOSA treatment. The present study suggests that LIPOSA pharmacopuncture can be a non-surgical alternative in the treatment of localized adiposity.

Pharmacopuncture of Taraxacum platycarpum extract reduces localized fat by regulating the lipolytic pathway.

Localized fat deposits are associated with health and aesthetic problems that mainly affect a large proportion of individuals. Recently, bioactive constituents of TP have been reported to affect lipid metabolism. In this study, we performed a network pharmacological analysis to assume potential lipolytic effects of TP and investigated the actual lipolytic effects of TP extract injection on local body fat and its underlying mechanism. Using the genes related to active compounds of TP, the network was constructed. Through the Functional Enrichment Analysis, Lipid Metabolism and Fatty Acid Metabolism were expected to be affiliated with the network, which implied possible lipolytic effects of TP. On the comparison between TP network and Obesity-related Gene Sets, about three-fourths of elements were in common with the gene sets, which indicated a high relevance between TP and obesity. Based on the genes in lipolysis-related pathways, Perilipin, CGI-58, ATGL, HSL and MGL were selected to identify the actual lipolytic effects of TP. TP injection reduced the inguinal fat weight. Also, the diameter of the adipocytes was decreased by the TP treatment in HFD-induced obese mice. In addition, TP suppressed lipid accumulation in differentiated 3T3-L1 adipocytes. Moreover, because the expression of Perilipin was increased, CGI-58, ATGL, HSL and MGL were markedly decreased. Furthermore, glycerol release was down-regulated by the TP treatment. TP exerted its lipolytic effects by regulating the lipolysis machinery through stimulation of lipases. Based on the present findings, TP is expected to be a potent component of injection lipolysis for removing localized body fat.

Palmul-Tang, a Korean Medicine, Promotes Bone Formation via BMP-2 Pathway in Osteoporosis.

Osteoporosis is a common skeletal disease in post-menopausal women. Palmul-tang, an herbal medicine, has been treated for gynecological disease such as anemia, anorexia, anti-fatigue, unspecified menstruation and female infertility in East Asia. In this study, ameliorative effects of Palmul-tang soft extracts (PMT), a Korean Medicine, on osteoporosis were investigated. Ovariectomized (OVX) osteoporotic ICR mice were intragastrically administrated PMT for 4 weeks. The level of bone mineral density (BMD) was analyzed in bone tissues by dual X-ray absorptiometry. The bone medullary cavity and deposition of collagen were investigated by histological analysis. In addition, the BMP-2 signaling-related molecules, osteoblastic differentiation and formation markers, were determined in femoral tissues. The levels of BMD and bone mineral content were significantly increased in tibia, femurs and LV by treatment of PMT. PMT replenished bone marrow cavity and increased collagen deposition in bone marrow cells of femur. In addition, administration of PMT recovered serum ALP, bALP, osteocalcin and calcium levels in osteoporotic mice. Moreover, PMT treatment up-regulated the expressions of BMP-2, RUNX2 and OSX with its downstream factors, ALP, OPN and BSP-1, in the femoral tissues. Taken together, PMT restored the bone minerals and improvement of bone integrity by bone-forming BMP-2 signaling pathway. These results demonstrate that PMT could be an ameliorative agent for osteoporosis.

Fat regulatory mechanisms of pine nut oil based on protein interaction network analysis.

BACKGROUND: Pine nut oil (PNO), a standardized and well-defined extract of Pinus koraiensis (Korean pine), has beneficial effects on wound healing, inflammatory diseases, and cancer. However, the explanation for the mechanism by which PNO reduces body fat remains uncertain. We performed a protein-protein interaction network (PPIN) analysis to explore the genes associated with pinolenic acid using the MEDILINE database from PubChem and PubMed. It was concluded through the PPIN analysis that PNO was involved in a neutral lipid biosynthetic process. PURPOSE: This study evaluated the effects of PNO predicted by the network analysis of fat accumulation in chronic obesity mouse models established by feeding a high fat diet (HFD) to C57BL/6J mice and explored potential mechanisms. METHODS: HFD mice were fed only HFD or HFD with PNO at 822 and 1644 mg/kg. After an oral administration of 7 weeks, several body weight and body fat-related parameters were examined, including the following: adipose weight, adipocyte size, serum lipid profiles, adipocyte expression of PPAR-γ, sterol regulatory element binding protein (SREBP)-1c, lipoprotein lipase (LPL) and leptin. RESULTS: We showed that oral administration of PNO to HFD mice reduces body fat weight, fat in tissue, white adipose tissue weight, and adipocyte size. The serum cholesterol was improved in the HFD mice treated with PNO. Additionally, PNO has significantly attenuated the HFD-induced changes in the adipose tissue expression of PPAR-γ, SREBP-1c, LPL, and leptin. CONCLUSIONS: The findings from this study based on the PPIN analysis suggest that PNO has potential as drug to reduce body fat through fat regulatory mechanisms by PPAR-γ and SREBP-1c.

Standardized hot water extract from the leaves of Hydrangea serrata (Thunb.) Ser. alleviates obesity via the AMPK pathway and modulation of the gut microbiota composition in high fat diet-induced obese mice.

Obesity is an increasing health problem worldwide as it is the major risk factor for metabolic diseases. In the present study, we investigated the anti-obesity effects of WHS by examining its effects on high fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed either a normal diet (ND) or a high fat diet (HFD) with or without WHS. At the end of the experiment, we observed the changes in their body weight and white adipose tissue (WAT) weight and lipid profiles in plasma. We performed western blot and histological analyses of WAT and liver to elucidate the molecular mechanisms of action. We also conducted fecal 16S rRNA analysis for investigating the gut microbiota. Our results indicated that pre- and post-oral administration of WHS significantly prevented body weight gain and reduced body fat weight in HFD-induced obese mice. In addition, WHS was found to improve adipocyte hypertrophy and liver fat accumulation by regulating the AMPK and AKT/mTOR pathways. WHS ameliorated hyperlipidemia by reducing total cholesterol and low-density lipoprotein (LDL) and decreased the energy metabolism-related hormones, leptin and insulin, in mouse plasma. Furthermore, we found that WHS modulated gut dysbiosis by normalizing HFD-induced changes. Taken together, our in vivo data implicate that WHS can be considered as a potential dietary supplement for alleviating obesity.

Derma-Hc, a New Developed Herbal Formula, Ameliorates Cutaneous Lichenification in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic cutaneous disorder that is characterized by severe eczematous inflammation, swelling, and lichenification. Activation of T helper (Th)-22 cells by allergens leads to epidermal hyperplasia with hyperkeratosis at the chronic phase of AD. Derma-Hc is composed of five natural herbs with anti-AD effects, such as Astragalus membranaceus BUNGE, Schizonepeta tenuifolia Briq., Cryptotympana pustulata Fabr., Angelica sinensis Diels, Arctium lappa L. In this study, the ameliorative effect of Derma-Hc on cutaneous lichenification in 2,4-dinitrochlorobenzne (DNCB)-induced AD was investigated. The dorsal skin of mice was sensitized with DNCB to induce AD-like skin lesions. The dermatitis score and frequency of scratching were evaluated. Thickness of epidermis and dermis was measured by staining with H&E. In addition, infiltration of the mast cell was observed by staining with toluidine blue. Then, desmosomal cadherin, DSC1 was examined by immunofluorescence. Pathological mechanisms involved in lichenification were analyzed in AD-like skin lesions and TNF-α + IFN-γ-treated with human keratinocytes including keratinocyte differentiation genes and JAK1-STAT3 signaling pathway with IL-22 by RT-PCR and western blotting. Topical treatment of Derma-Hc improved AD-like symptoms such as dryness, edema and lichenefication and decreased the number of scratches. Histopathological analysis demonstrated that Derma-Hc significantly inhibited epidermal hyperplasia, hyperkeratosis, and mast cells infiltration. In addition, the level of DSC1 was highly expressed in the epidermis by Derma-Hc. Moreover, mRNA expression level of FLG, an epidermal differentiation complex gene, was recovered by Derma-Hc treatment. KLK5 and KLK7 were markedly reduced to normalize keratinocyte differentiation in dorsal skin tissues and human keratinocytes. On the other hand, Derma-Hc restored expression level of SPINK5. In addition, Derma-Hc inhibited IL-22 via the blockade of JAK1-STAT3 signal pathway. Taken together, Derma-Hc, a natural herbal formula, regulated keratinocyte differentiation and inhibited epidermal hyperplasia with hyperkeratosis. Therefore, Derma-Hc could be a promising candidate for treating chronic AD through modulating signaling of IL-22-associated skin lichenification.

Anti-Inflammatory Effects of Sosiho-Tang, a Traditional Herbal Formula, on Acute Lung Injury in LPS-Sensitized Mice and -Raw 264.7 Cells.

Acute lung injury (ALI) is a series of syndromes with persistent inflammation and abnormally increased vascular permeability. Sosiho-tang (SSHT), a traditional herbal formula consisting of a mixture of seven herbs, has been used to treat allergic reactions and chronic hepatitis disease in East Asia. In this study, we determined whether SSHT has an inhibitory effect against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. 0.05, 0.55, and 5.55 mg/kg of SSHT were orally administered to C57BL/6J mice for 7 days prior to the administration of LPS. After 2 h of LPS sensitization, lung tissues were collected to confirm the lung histology and ALI-related inflammatory factors. SSHT ameliorated the LPS-induced alveolar hemorrhage, alveolar wall thickening, and the shrinkage of the alveolar spaces in the ALI mice model. Proinflammatory cytokines including IL-6, TNF-α, and IFN-γ in the lung tissue were significantly regulated in the SSHT-treated groups compared to the LPS only-treated group. Also, increases of IL-6 and TNF-α and decrease of IFN-γ expressions were dose-dependently modulated by SSHT treatment in LPS-induced raw 264.7 cells. Additionally, the translocation of NF-κB into nucleus and phosphorylation of mitogen-activated protein (MAP) kinase were significantly attenuated by the treatment of SSHT in LPS-sensitized ALI mice. SSHT showed anti-inflammatory activities by inhibiting proinflammatory cytokines and NF-κB signaling in LPS-induced ALI. This study demonstrates that SSHT has preventive effects on LPS-induced ALI by regulating inflammatory responses as an alternative for treating lung diseases.

Lipolytic and Lipophagic Effects of Pinellia ternata Pharmacopuncture on Localized Adiposity.

Localized adiposity is not only a common aesthetic issue but also a health risk factor. Pharmacopuncture can be a therapeutic option for the imbalance of regional fat distribution. The tuber of Pinellia ternata has been prescribed as antitussive and expectorant as a traditional Korean medicine. This study investigated the effects of pharmacopuncture with P. ternata water extract (PT) on localized adiposity. Male C57BL/6J mice were fed on a high-fat diet (HFD) for 6 weeks. 100 µL of 10 mg/mL of PT was injected into the left-side inguinal fat pad, while saline was injected into the right-side inguinal fat pad as self-control. Treatments were performed 3 times per week for 4 weeks. The inguinal fat weight was analyzed by dual-energy X-ray absorptiometry. PT pharmacopuncture significantly decreased the weight of the inguinal fat pad. The adipocyte size was reduced with increases of lipolytic enzymes and lipophagy-related factors by PT pharmacopuncture. There was marked inhibition of lipid accumulation content in 3T3-L1 adipocytes by PT treatment. The expressions of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), autophagy-related gene (ATG) 5, ATG7, and LC3 were markedly increased by PT treatments in vivo and in vitro. This study suggests that pharmacopuncture of Pinellia ternata has ameliorative effects on adiposity by lipid catabolic effects via activating both lipolysis and lipophagy in a localized region.

Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway.

BACKGROUND: The fruit of Zanthoxylum piperitum (ZP) is an herbal medicine as well as a spice agent in Asia to treat carminative, stomachic, anthelmintic and degenerative diseases. Z. piperitum was reported to have anti-oxidant, anti-inflammatory, anti-osteoarthritic and osteosarcoma proliferation-control effects. PURPOSE AND STUDY DESIGN: This study was conducted to determine the anti-osteoporotic effects and mechanisms of action of ZP. METHODS: Female ICR mice underwent ovariectomies (OVX) and were orally administered ZP at 1, 10 and 100 mg/kg for 6 weeks. The femoral and tibial bones were assessed by dual-energy X-ray absorptiometry and histology to analyze the bone mineral density (BMD) and the number of osteoclasts. Raw 264.7 cells were stimulated by 100 ng/ml receptor activator of nuclear factor-κB ligand (RANKL) for 7 days in the presence of ZP. RANKL-induced signaling molecules were analyzed in osteoclasts. RESULTS: The levels of femoral and tibial BMD were significantly increased by ZP administration. Serum biomarkers such as osteocalcin, calcium, alkaline phosphatase and bone-specific alkaline phosphatase concentrations were markedly recovered to normal levels in ZP-treated osteoporotic mice. In addition, the number of osteoclasts in the head, trochanter and body of the femur was obviously decreased in the ZP treatment groups. Moreover, ZP treated-cells showed a reduction in the number of TRAP-positive multinuclear cells in RANKL-stimulated Raw 264.7 cells. ZP decreased the RANKL-activated NFATc1 and c-fos, transcription factors of osteoclast formation. The nuclear translocation of NF-κB and phosphorylation of ERK42/44 were inhibited by the ZP treatment in RANKL-induced osteoclasts. CONCLUSION: Collectively, ZP exerts its inhibitory effect against bone resorption by regulating RANKL-mediated c-fos/NFATc1/NF-κB in osteoclast. ZP may prove to be a therapeutic agent for osteoporosis.

Ameliorative effects of Osteo-F, a newly developed herbal formula, on osteoporosis via activation of bone formation.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Schizandra chinensis and Lycium chinense, and the root of Eucommia ulmoides, components of Osteo-F, has traditionally been used for treating bone diseases in Korean Medicine. AIM OF THE STUDY: The exact role and underlying mechanism of Osteo-F herbal formula on bone formation in osteoporosis was investigated in the present study. MATERIALS AND METHODS: OVX mice were treated with 0.9, 9 and 90 mg/kg of Osteo-F for 4 weeks. Bone tissues including fourth to sixth lumbar vertebrae (LV) and femur were collected to analyze the bone mineral density (BMD). In addition, serum biomarkers were estimated by enzyme-linked immunosorbent assay. The expressions of collagen, BMP-2 and osteopontin were determined in tibia to clarify the bone anabolic effects of Osteo-F in osteoporosis. RESULTS: The levels of BMD in both of fourth to sixth LV and femur were significantly increased by Osteo-F treatment in OVX mice. Bone mineral content (BMC) was also elevated in Osteo-F-treated LV and femoral bone tissues. In addition, serum osteocalcin was markedly increased by Osteo-F in osteoporotic mice. Serum ALP and bALP levels were neutralized in Osteo-F 90 mg/kg-administered mice. Furthermore, Osteo-F treatment dramatically increased the mRNA expressions of collagen type I, BMP-2 and OPN in tibial bone specimens. CONCLUSIONS: Osteo-F ameliorated bone loss by increasing bone forming molecules including BMP-2 and OPN in osteoporosis. Osteo-F, a newly developed herbal formula, may be an alternative material for the management of osteoporosis with bone anabolic effects.

Ameliorative and Synergic Effects of Derma-H, a New Herbal Formula, on Allergic Contact Dermatitis.

Allergic contact dermatitis (ACD) is characterized by itching, skin inflammation, and allergic responses caused by release of immunoglobulin E and T helper 2-specific cytokines. The aim of this study is to investigate the ameliorative and synergic effects of herbal formula, Derma-H, containing Astragalus membranaceus Fisch. ex Bunge (AM) and Nepeta tenuifolia Benth (NT) which have been used as traditional medicinal herbs for the cure of dryness, edema, and pruritus. 2,4-Dinitrochlorobenzene (DNCB) was applied for ACD induction. AM, NT, and a mixture of AM and NT was topically applied to skin lesions for 11 days. Dermatitis score and number of scratches were significantly diminished in AM, NT, and AM + NT (Derma-H)-treated groups. Especially, Derma-H was more effective than single treatment of AM and NT on skin hyperplasia and mast cell infiltration. Also, NGF expression decreased by NT and a mixture of AM and NT. Additionally, series of TrkA, Raf-1, MEK, and ERK were significantly inhibited by topical AM and NT application. Those findings suggested AM and NT treatment has a synergic effect on DNCB-induced ACD in mice.

Anti-inflammatory effects of Samsoeum, a Korean medicine for health insurance, on chronic bronchitis caused by lipopolysaccharide in rats.

BACKGROUND: Samsoeum (SSE), a Korean medicine, has been used to treat upper respiratory infection including residual coughs after catching a cold, and colds in patients with gastrointestinal disorder. In this study, we investigated the inhibitory effect of SSE against lipopolysaccharide (LPS)-induced bronchitis and characterized its optimal dosing range based on the improvement of SSE concentrations. MATERIALS AND METHODS: Male Sprague Dawley rats were intra-nasally administered LPS on day 0, 3 and 6. 2 g kg-1 dose of SSE for rat was determined by the human equivalent dose formula and orally administered once a day from day 3 to day 6. To clarify the optimal administration dose of SSE, various doses including 0.5 (1/4 fold), 1 (1/2 fold), 6 (3 fold), 12 (6 fold), 24 (12 fold) and 36 g kg-1 (18 fold) were also orally administered. In addition, the molecular mechanism of SSE in mucin hyperproduction was investigated in LPS-sensitized A549 cells. RESULTS: Oral administration of SSE ameliorated alveolar wall thickening and inflammatory cell infiltration of lung tissues in LPS-induced bronchitis at doses of 1/4 fold, 1/2 fold and 1 fold. The total cell and neutrophil numbers in bronchoalveolar lavage fluid (BALF) were reduced in the SSE-treated groups compared with the LPS group. In addition, 0.5, 1 and 2 g kg-1 of SSE suppressed LPS-induced mucin glycoprotein 5AC (MUC5AC) production in BALF. Furthermore, SSE treatment significantly inhibited the pro-inflammatory cytokines, resulting in the decrease of MUC5AC production by the JAK1/STAT6 signaling pathway. CONCLUSIONS: 1, 2 and 6 g kg-1 of SSE ameliorated chronic bronchitis by inhibiting LPS-induced neutrophil infiltration and MUC5AC release in BALF. These findings suggested that SSE with 0.5-3-fold of general daily intake dose would be a therapeutic agent for chronic bronchitis.