Securinega suffruticosa extract alleviates atopy-like lesions in NC/Nga mice via inhibition of the JAK1-STAT1/3 pathway.

Securinega suffruticosa (SS) has well-known antioxidant, anti-vascular inflammation, and anti-bone resorption effects; however, the effects of SS in atopic dermatitis (AD) remain unknown. We examined the effects of SS on AD via application of Dermatophagoides farinae extract (DfE) to the ears and skin of NC/Nga mice. As a result of SS administration, DfE-induced AD mice had reduced ear thickness, epidermal thickness, scratching behavior, and transepidermal water loss. The serum levels of immunoglobulin E and thymic interstitial lymphopoietin (TSLP) were reduced by SS application. SS decreased mast cell and eosinophil recruitment to skin lesions. Phosphorylation of signal transducer and activation of transcription (STAT)1, STAT3, and Janus kinase 1 were reduced in the skin tissue of SS-administered mice, and downregulated filaggrin was restored. SS reduced the levels of interleukin-6, regulated on activation, normal T cell expressed and secreted chemokine, and TSLP in interferon-γ/tumor necrosis factor-α-induced keratinocytes. The main components of SS were rutin and geraniin. These study results indicated that SS extract attenuated AD and has potential as a therapeutic natural product candidate for AD.

Photoprotective Effects of Processed Ginseng Leaf Administration against UVB-Induced Skin Damage in Hairless Mice.

Although ginseng leaves contain a larger amount of ginsenosides than the roots, studies on the protective effect of oral administration of ginseng leaves against photoaging are lacking. Processed ginseng leaves (PGL) prepared by acid reaction to increase effective ginsenoside content showed higher levels of Rg3 (29.35 mg/g) and Rk1 (35.16 mg/g) than ginseng leaves (Rg3 (2.14 mg/g) and Rk1 (ND)), and ginsenosides Rg3 and Rk1 were evaluated as active ingredients that protected human keratinocytes against UVB-induced cell damage by increasing cell proliferation and decreasing matrix metalloproteinase (MMP)-2 and 9 secretion. Herein, the effect of oral PGL administration (50, 100, or 200 mg/kg, daily) against photoaging in HR-1 hairless mice was assessed by measuring wrinkle depth, epidermal thickness, and trans-epidermal water loss for 16 weeks. The PGL treatment group showed reduced skin wrinkles, inhibited MMP-2 and MMP-9 expression, and decreased IL-6 and cyclooxygenase-2 levels. These data suggest that oral PGL administration inhibits photoaging by inhibiting the expression of MMPs, which degrade collagen, and inhibiting cytokines, which induce inflammatory responses. These results reveal that ginseng leaves processed by acid reaction may serve as potential functional materials with anti-photoaging activities.

Protective Effects of Glycine soja Leaf and Stem Extract against Chondrocyte Inflammation and Osteoarthritis.

Wild soybean, also known as Glycine soja Sieb. et Zucc. (GS), has long been known for its various health benefits. Although various pharmacological effects of G. soja have been studied, the effects of GS leaf and stem (GSLS) on osteoarthritis (OA) have not been evaluated. Here, we examined the anti-inflammatory effects of GSLS in interleukin-1ß (IL-1ß)-stimulated SW1353 human chondrocytes. GSLS inhibited the expression of inflammatory cytokines and matrix metalloproteinases and ameliorated the degradation of collagen type II in IL-1ß-stimulated chondrocytes. Furthermore, GSLS played a protective role in chondrocytes by inhibiting the activation of NF-κB. In addition, our in vivo study demonstrated that GSLS ameliorated pain and reversed cartilage degeneration in joints by inhibiting inflammatory responses in a monosodium iodoacetate (MIA)-induced OA rat model. GSLS remarkably reduced the MIA-induced OA symptoms, such as joint pain, and decreased the serum levels of proinflammatory mediators, cytokines, and matrix metalloproteinases (MMPs). Our findings show that GSLS exerts anti-osteoarthritic effects and reduces pain and cartilage degeneration by downregulating inflammation, suggesting that it is a useful therapeutic candidate for OA.

Potent Xanthine Oxidase Inhibitory Activity of Constituents of Agastache rugosa (Fisch. and C.A.Mey.) Kuntze.

The aerial parts of Agastache rugosa are used as a food material and traditional medicine in Asia. A 50% ethanol extract exhibited potent xanthine oxidase (XO) inhibitory activity (IC50 = 32.4 µg/mL). To investigate the major components responsible for this effect, seven known compounds were identified from A. rugosa; among these, salvianolic acid B (2) was isolated from this plant for the first time. Moreover, acacetin (7) exhibited the most potent inhibitory activity with an IC50 value of 0.58 µM, lower than that of allopurinol (IC50 = 4.2 µM), which is commonly used as a XO inhibitor. Comparative activity screening revealed that the C6-bonded monosaccharides (3) or sugars substituted with acetyl or malonyl groups (4-6) are critical for XO inhibition when converted to aglycone (7). The most potent inhibitor (7) in the A. rugosa extract (ARE) exhibited mixed-type inhibition kinetics and reversible inhibition toward XO. Furthermore, the hydrolysis of ARE almost converted to an inhibitor (7), which displayed the highest efficacy; UPLC-qTof MS revealed an increased content, up to five times more compared with that before treatment. This study will contribute to the enhancement in the industrial value of ARE hydrolysates as a functional ingredient and natural drug toward the management of hyperuricemia and treatment of gout.

Connarus semidecandrus Jack Exerts Anti-Alopecia Effects by Targeting 5α-Reductase Activity and an Intrinsic Apoptotic Pathway.

There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair-skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.

Synergistic Impacts of Alpinia oxyphylla Seed Extract and Allopurinol against Experimental Hyperuricemia.

In traditional medicine, Alpinia oxyphylla Miquel seed has been used to treat gout and hyperuricemia-related symptoms by enhancing kidney functions. Allopurinol is the most commonly used drug to treat hyperuricemia; however, the drug has many adverse effects. Combining allopurinol with another compound could reduce the need for high doses and result in improved safety. We investigated the possible synergistic effects of Alpinia oxyphylla seed extract (AE) and allopurinol in decreasing urate concentrations in rats with potassium oxonate-induced hyperuricemia. This study evaluated the effects of allopurinol combined with AE on levels of serum urate, blood urea nitrogen (BUN), and creatinine in a hyperuricemic rat model. The effects of allopurinol plus AE on xanthine oxidase (XOD) activity and urate uptake were measured. The concomitant administration of allopurinol and AE normalized serum urate and reduced BUN and creatinine. The attenuation of hyperuricemia-induced impaired kidney function was related to downregulation of renal urate transporter 1 and upregulation of renal organic anion transporter 1, with inhibition of serum and hepatic XOD activities. The antihyperuricemic effects of allopurinol were enhanced when combined with AE. These results suggested that the combined use of allopurinol and AE may have clinical efficacy in treating hyperuricemia.

Duchesnea indica Extract Ameliorates LPS-Induced Septic Shock in Mice.

Objective: Duchesnea indica has been reported for its anti-inflammatory properties. However, its efficacy in sepsis has yet to be reported. In this study, we studied the ability of Duchesnea indica extract (DIE) to rescue mice from septic shock and sepsis. Methods: In vitro studies included the measurement of secreted nitric oxide, cell viability, gene and protein expression via real-time polymerase chain reaction and western blot, and confocal microscopy in RAW 264.7 cells. In vivo studies include a model of septic shock and sepsis in BALB/c mice induced by a lethal and sub-lethal dose of lipopolysaccharide (LPS). Results: DIE suppressed the expression of proinflammatory cytokines induced by LPS and prevented the translocation of NFκB into the nucleus of RAW 264.7 cells. It also prevented reactive oxygen species damage induced by LPS in murine bone marrow-derived macrophages. Models of sepsis and septic shock were established in BALB/c mice and DIE-rescued mice from septic shock. DIE also reversed the increase in tumor necrosis factor-α and nitrite levels in the serum of mice induced with sepsis. DIE also prevented the translocation of NFκB from the cytosol into the nucleus in murine lungs. Histopathological damage induced by sepsis was reversed in the testis, liver, and lungs of mice. Conclusion: In conclusion, DIE is a suitable candidate for development as a therapeutic agent for sepsis.

Anti-Inflammatory and Analgesic Effects of Schisandra chinensis Leaf Extracts and Monosodium Iodoacetate-Induced Osteoarthritis in Rats and Acetic Acid-Induced Writhing in Mice.

In this study, we aimed to determine the anti-inflammatory and antinociceptive activities of Schisandra chinensis leaf extracts (SCLE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, an acetic acid-induced mouse model of writhing, and a monosodium iodoacetate (MIA)-induced rat model of osteoarthritis (OA). In LPS-stimulated RAW264.7 cells, a 100 µg/mL dose of SCLE significantly reduced the production of nitric oxide (NO), interleukin-1ß (IL-1ß), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2). Acetic acid-induced writhing responses in mice that quantitatively determine pain were significantly inhibited by SCLE treatment. In addition, SCLE significantly decreased the MIA-induced elevation in OA symptoms, the expression levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases, and cartilage damage in the serum and joint tissues. Our data demonstrated that SCLE exerts anti-osteoarthritic effects by regulating inflammation and pain and can be a useful therapeutic candidate against OA.

Antioxidant Capacity of Potentilla paradoxa Nutt. and Its Beneficial Effects Related to Anti-Aging in HaCaT and B16F10 Cells.

Skin aging is a natural process influenced by intrinsic and extrinsic factors, and many skin anti-aging strategies have been developed. Plants from the genus Potentilla has been used in Europe and Asia to treat various diseases. Potentilla paradoxa Nutt. has been used as a traditional medicinal herb in China and has recently been shown to have anti-inflammatory effects. Despite the biological and pharmacological potential of Potentilla paradoxa Nutt., its skin anti-aging effects remain unclear. Therefore, this study evaluated the free radical scavenging, moisturizing, anti-melanogenic, and wound-healing effects of an ethanol extract of Potentilla paradoxa Nutt. (Pp-EE). Pp-EE was found to contain phenolics and flavonoids and exhibits in vitro antioxidant activities. α-Linolenic acid was found to be a major component of Pp-EE on gas chromatography-mass spectrometry. Pp-EE promoted the expression of hyaluronic acid (HA) synthesis-related enzymes and suppressed the expression of HA degradation-related enzymes in keratinocytes, so it may increase skin hydration. Pp-EE also showed inhibitory effects on the production and secretion of melanin in melanocytes. In a scratch assay, Pp-EE improved skin wound healing. Taken together, Pp-EE has several effects that may delay skin aging, suggesting its potential benefits as a natural ingredient in cosmetic or pharmaceutical products.

Inhibitory effects of modified gamgil-tang in a particulate matter-induced lung injury mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The modified gamgil-tang (GGX) is a mixture of four herbal medicine including Platycodi Radix, Glycyrrhizae Radix, Lonicerae Flos and Mori Radicis Cortex which has been traditionally used to treat lung and airway diseases to relieve symptoms like sore throat, cough, and sputum in Korea. Its major component chlorogenic acid had been reported to have antioxidant, antibacterial, hepatoprotective, cardioprotective, anti-inflammatory, antiviral, and anti-microbial activity. AIM OF THE STUDY: To identify the inhibitory effect of GGX in a particulate matter (PM) induced lung injury mouse model. MATERIALS AND METHODS: We evaluated NO production, the release of TNF-α and IFN-γ in PM-induced MH-S cells, and the number of neutrophils, immune cell subtypes, and the secretion of TNF-α, IL-17, CXCL-1, MIP-2 in the PM-stimulated mouse model to assess the inhibitory effect of GGX against PM. In addition, as exposure to PM increases respiratory symptoms, typically cough and sputum, we attempted to evaluate the antitussive and expectorant activities of GGX. RESULTS: Our study provided evidence that GGX has inhibitory effects in PM-induced lung injury by inhibiting the increase in neutrophil and inflammatory mediators, deactivating T cells, and ameliorating lung tissue damage. Notably, GGX reduced PM-induced neutrophilic inflammation by attenuating the number of neutrophils and regulating the secretion of neutrophil-related cytokines and chemokines, such as TNF-α, IL-17, MIP2, and CXCL-1. In addition, GGX demonstrated an antitussive activity by significantly reducing citric acid-induced cough frequency and delaying the latent period and expectorant activities by the increased phenol red secretion compared to the control group. CONCLUSIONS: GGX is expected to be an effective herbal remedy to prevent PM-induced respiratory disease.

Saengmaeksan, a traditional herbal formulation consisting of Panax ginseng, ameliorates hyperuricemia by inhibiting xanthine oxidase activity and enhancing urate excretion in rats.

BACKGROUND: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, Panax ginseng, Schisandra chinensis, and Liriope platyphylla. SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown. METHODS: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on in vitro XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC). RESULTS: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1ß levels in both the serum and kidneys. SMS-E inhibited both in vitro XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W. CONCLUSION: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

Eggshell Membrane Ameliorates Hyperuricemia by Increasing Urate Excretion in Potassium Oxonate-Injected Rats.

Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1ß levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.

Matricaria chamomilla (Chamomile) Ameliorates Muscle Atrophy in Mice by Targeting Protein Catalytic Pathways, Myogenesis, and Mitochondrial Dysfunction.

Muscle atrophy, or loss of skeletal muscle, is caused by aging, malnutrition, immobility through injury, or diseases such as cancer. Chamomile (Matricaria chamomilla L.) contains various active components, including flavonoids, sesquiterpenes, polyacetylenes, and coumarins, and is used in various herbal medicines in the European Pharmacopoeia. In this study, we investigated the effects of ethanol extract of chamomile [Formula: see text](MC) on muscle wasting and its mechanism of action. Mice with dexamethasone (DEX)-induced muscle atrophy were orally administered MC (100, 200, and 300 mg/kg) for 4 weeks. Micro-computed tomography analysis showed that MC (200 and 300 mg/kg) significantly recovered DEX-induced loss of muscle volume, density, and weight and MC-treated DEX-induced mice also showed increased moving distance and grip strength. MC suppressed the mRNA level of muscle RING finger 1 (MuRF1) while increasing the expression of mitochondrial transcription factor A (TFAM), MyoD, and Myogenin-1. We found 25 peaks in MC samples through HPLC analysis and identified 6 peaks by comparison with a profile of standard compounds: chlorogenic acid (CGA), luteolin-7-O-glucoside (L7G), patulitrin, apigenin-7-O-glucoside (A7G), herniarin, and (E)-tonghaosu. Of these components, the gene expression of MyoD was significantly augmented by patulitrin, herniarin, CGA, and L7G in C2C12 cells, while Myogenin-1 gene expression was increased by A7G, patulitrin, herniarin, CGA, and L7G. Moreover, TFAM gene expression and phosphorylation of AKT were increased by all six ingredients. Based on our results, we suggest MC for use as a supplement or remedy for muscle wasting, including cachexia and sarcopenia.

Corrigendum to "A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium induced colitis in mice" [J Ginseng Res 44 (2020) 833-842].

[This corrects the article DOI: 10.1016/j.jgr.2020.02.003.].

Chondroprotective effect of Alpinia oxyphylla extract in experimentally induced cartilage degradation in rabbit articular cartilage explants.

Alpinia oxyphylla is a widely used medicinal herb for diarrhea, gastralgia, tumors, hypertention, and cerebrovascular disorders. Here, we evaluated the chondroprotective effect of A. oxyphylla dried fruit ethanol extract (AOE) against cartilage degradation in rabbit articular cartilage explants. Treatment of interleukin-1α (IL-1α) and plasminogen increased degraded collagen release in culture supernatants, but pretreatment of AOE (50, 100, 200 µg/ml) inhibited the collagen release in dose-dependent manner. To examine the mechanism of action of AOE on chondroprotection, the level of matrix metalloproteinases-3 (MMP-3), matrix metalloproteinases-13 (MMP-13), tissue inhibitor of metalloprotease-1 (TIMP-1), and inflammatory mediators like prostaglandin E2 (PGE2 ) and nitric oxide (NO) was evaluated. AOE inhibited upregulation of MMP-3 and MMP-13 and downregulation of TIMP-1 and also reduced increase of PGE2 and NO level induced by exposure of IL-1α and plasminogen. These results indicate that AOE show chondroprotective effect through inhibiting collagen degradation via regulating MMPs, TIMP-1, and inflammatory mediators. PRACTICAL APPLICATIONS: Osteoarthritis (OA) is a one of the most common chronic disorders in elderly persons. Because the regenerative power of joint articular cartilage is very low, treatment of OA is difficult to expect complete recovery. Therefore, there is a need to develop a therapeutic agent that can safely and effectively inhibit the cartilage destruction. For the first time, we exhibited the inhibitory effect of AOE on collagen degradation through regulating MMPs and TIMP-1 in articular cartilage explants. These findings support AOE could be used as herbal therapeutic application for protecting articular cartilage to prevent OA.

Comparative Study of Anti-Gouty Arthritis Effects of Sam-Myo-Whan according to Extraction Solvents.

Sam-Myo-Whan (SMW) has been used in Korean and Chinese traditional medicine to help treat gout, by reducing swelling and inflammation and relieving pain. This study compared the effects of SMW extracted by using different solvents, water (SMWW) and 30% EtOH (SMWE), in the treatment of gouty arthritis. To this end, we analyzed the main components of SMWW and SMWE, using high-performance liquid chromatography (HPLC). Anti-hyperuricemic activity was evaluated by measuring serum uric acid levels in hyperuricemic rats. The effects of SMWW and SMWE on swelling, pain, and inflammation in gouty arthritis were investigated by measuring affected limb swelling and weight-bearing, as well as by enzyme-linked immunosorbent assays, to assess the levels of proinflammatory cytokines and myeloperoxidase (MPO). In potassium oxonate (PO)-induced hyperuricemic rats, SMWW and SMWE both significantly decreased serum uric acid to similar levels. In monosodium urate (MSU)-induced gouty arthritis mice, SMWE more efficiently decreased paw swelling and attenuated joint pain compare to SMWW. Moreover, SMWE and SMWW suppressed the level of inflammation by downregulating proinflammatory cytokines (interleukin-1ß, tumor necrosis factor-α, and interleukin-6) and MPO activity. HPLC analysis further revealed that berberine represented one of the major active ingredients demonstrating the greatest change in concentration between SMWW and SMWE. Our data demonstrate that SMWE retains a more effective therapeutic concentration compared to SMWW, in a mouse model of gouty arthritis.

Effect of Jakyakgamcho-Tang Extracts on H2O2-Induced C2C12 Myoblasts.

Oxidative stress is a major contributor to muscle aging and loss of muscle tissue. Jakyakgamcho-tang (JGT) has been used in traditional Eastern medicine to treat muscle pain. Here, we compared the total phenolic and flavonoid contents in 30% ethanol and water extracts of JGT and tested the preventive effects against oxidative stress (hydrogen peroxide)-induced cell death in murine C2C12 skeletal muscle cells. The total phenolic content and total flavonoid content in 30% ethanol extracts of JGT were higher than those of water extracts of JGT. Ethanol extracts of JGT (JGT-E) had stronger antioxidant activities of 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2'-diphenyl-1-picrylhydrazyl-scavenging activity (DPPH) than water extracts of JGT (JGT-W). JGT-E contained 19-53% (1.8 to 4.9-fold) more active compounds (i.e., albiflorin, liquiritin, pentagalloylglucose, isoliquiritin apioside, isoliquiritin, liquiritigenin, and glycyrrhizin) than JGT-W. The ethanol extracts of JGT inhibited hydrogen peroxide-induced cell death and intracellular reactive oxygen species generation more effectively than the water extract of JGT in a dose-dependent manner. For the first time, these results suggest that ethanol extract of JGT is relatively more efficacious at protecting against oxidative stress-induced muscle cell death.

Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway.

Prasiola japonica possesses several biological activities. However, reports on the anti-inflammatory activities and molecular mechanisms of its different solvent fractions remain limited. In this study, we investigated the potential anti-inflammatory activities of P. japonica ethanol extract (Pj-EE) and four solvent fractions of Pj-EE made with hexane (Pj-EE-HF), chloroform (Pj-EE-CF), butanol (Pj-EE-BF), or water (Pj-EE-WF) in both in vitro (LPS-induced macrophage-like RAW264.7 cells) and in vivo (carrageenan-induced acute paw edema mouse models) experiments. The most active solvent fraction was selected for further analysis. Various in vitro and in vivo assessments, including nitric oxide (NO), cytokines, luciferase assays, real-time polymerase chain reactions, and immunoblotting analyses were performed to evaluate the underlying mechanisms. In addition, the phytochemical constituents were characterized by Liquid chromatography-tandem mass spectrometry. In in vitro studies, the highest inhibition of NO production was observed in Pj-EE-CF. Further examination revealed that Pj-EE-CF decreased the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells and suppressed subsequent AP-1-luciferase activity by inhibition of phosphorylation events in the AP-1 signaling pathway. Pj-EE-CF treatment also demonstrated the strongest reduction in thickness and volume of carrageenan-induced paw edema, while Pj-EE-BF showed the lowest activity. Furthermore, Pj-EE-CF also reduced gene expression and cytokines production in tissue lysates of carrageenan-induced paw edema. These findings support and validate the evidence that Pj-EE, and especially Pj-EE-CF, could be a good natural source for an anti-inflammatory agent that targets the AP1 pathway.

Dojuksan ameliorates tubulointerstitial fibrosis through irisin-mediated muscle-kidney crosstalk.

BACKGROUND: Sarcopenia progresses in chronic kidney disease (CKD) and is positively correlated with mortality in end-stage kidney disease patients. Circulating irisin, an exercise-induced myokine, gradually decreases during CKD stage progression. Irisin inhibits the progression of kidney fibrosis, which is the final common outcome of CKD. Our preliminary study with C2C12 cells showed that Dojuksan, a herbal decoction, increases the expression of PGC1α (a regulator of irisin) and FNDC5 (a precursor of irisin). HYPOTHESIS: Dojuksan may increase circulating irisin and prevent the progression of kidney fibrosis. STUDY DESIGN AND METHODS: Unilateral ureteral obstruction (UUO) was performed on seven-week-old male C57BL/6 mice to induce kidney tubulointerstitial fibrosis. Dojuksan (50, 100, or 200 mg/kg/day) or losartan (1.5 mg/kg/day), a standard clinical treatment for CKD, was administered orally one day prior to surgery and continued for seven days thereafter. To determine the role of irisin released from muscles, TGFß-stimulated murine proximal tubular epithelial cells (mProx24 cells) were treated with conditioned media (CM) from Dojuksan-treated C2C12 muscle cells transfected with FNDC5 siRNA. RESULTS: UUO mice exhibited muscle wasting along with progressive kidney injury. Similar to losartan, Dojuksan ameliorated kidney inflammation and fibrosis in UUO mice. Dojuksan, but not losartan, increased plasma irisin concentration in UUO mice. Dojuksan significantly increased basal FNDC5 expression and inhibited TNFα-induced and indoxyl sulfate-induced FNDC5 down-regulation in C2C12 cells. The TGFß-induced collagen I (COL1) up-regulation in mProx24 cells was effectively inhibited by CM from C2C12 cells after Dojuksan treatment. Moreover, irisin inhibited TGFß-induced COL1 in mProx24 cells, which was not affected by CM from C2C12 cells transfected with FNDC5 siRNA. CONCLUSION: Dojuksan ameliorates kidney fibrosis through irisin-mediated muscle-kidney crosstalk, suggesting that Dojuksan may be used as an alternative therapeutic agent against CKD.

Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality.

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.