Methylsulfonylmethane promotes melanogenesis via activation of JNK in Mel-Ab cells.

OBJECTIVE: Methylsulfonylmethane (MSM), which contains organic sulphur, has been used for a long time as a medicinal ingredient because of its benefits to human health. MSM is reported to be protective against certain skin disorders, but it is unknown whether it affects melanin synthesis. Therefore, in our current research, we examined the possibility of MSM controlling the production of melanin in Mel-Ab melanocytes. METHODS: In Mel-Ab cells, melanin contents and tyrosinase activities were assessed and quantified. The expression of microphthalmia-associated transcription factor (MITF) and tyrosinase was evaluated using western blot analysis, while MSM-induced signalling pathways were investigated. RESULTS: The MSM treatment significantly resulted in a dose-dependent increase in melanin production. Furthermore, MSM elevated melanin-related proteins, including MITF and tyrosinase. However, the rate-limiting enzyme of melanin production, tyrosinase, was not directly influenced by it. Therefore, we investigated potential melanogenesis-related signalling pathways that may have been triggered by MSM. Our findings showed that MSM did not influence the signalling pathways associated with glycogen synthase kinase 3ß, cAMP response-element binding protein, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase. However, MSM phosphorylated c-Jun N-terminal kinases/stress-activated protein kinase (JNK/SAPK), which is known to induce melanogenesis. SP600125, a specific JNK inhibitor, inhibited MSM-induced melanogenesis. CONCLUSION: Taken together, our study indicates that MSM induces melanin synthesis and may serve as a therapeutic option for hypopigmentary skin disorders such as vitiligo.

Investigation of Drug-Interaction Potential for Arthritis Dietary Supplements: Chondroitin Sulfate, Glucosamine, and Methylsulfonylmethane.

Osteoarthritis is one of the leading conditions that promote the consumption of these dietary supplements. Chondroitin sulfate, glucosamine, and methylsulfonylmethane are among the prominent alternative treatments for osteoarthritis. In this study, these dietary supplements were incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes, and the formation of marker metabolites was measured to investigate their inhibitory potential on cytochrome P450 enzyme activities. The results revealed no significant inhibitory effects on seven CYPs, consistent with established related research data. Therefore, these substances are anticipated to have a low potential for cytochrome P450-mediated drug interactions with osteoarthritis medications that are likely to be co-administered. However, given the previous reports of interaction cases involving glucosamine, caution is advised regarding dietary supplement-drug interactions.

[Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D3 and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee joint].

AIM: To evaluate the efficacy of Artneo (AN) in comparison with a combination of glucosamine hydrochloride and chondroitin sulfate (GC) in patients with osteoarthritis (OA) of the knee joint (KJ). MATERIALS AND METHODS: 70 patients with stages I-III of primary knee OA were randomized into 2 groups. Participants in the 1st (n=35) took AN 1 caps/day, in the 2nd (n=35) GC according to the standard regimen. After 7, 30, 90, 180 days, the Lequesne index (severity of OA), pain when moving according to VAS, WOMAC score were assessed, after 1, 3, 6 months - quality of life SF-36 and morning stiffness, after 6 months - MRI with T2 mapping, laboratory safety indicators. RESULTS: Over the course of 6 months of use, an improvement in the WOMAC index and a decrease in pain were observed without intergroup differences, and a greater decrease in stiffness in the AN group. After 3 months, the severity of OA decreased from moderate to mild in the AN group and was significantly lower compared to the GC group; quality of life (physical component of SF-36) was higher in the AN group. After 6 months, there was an improvement in cartilage ultrastructure (T2 relaxation time) in both groups and a more pronounced reduction of the synovitis area (MRI) in the AN group (2.95 and 1.37 times in the AN and GC group, respectively). There were no clinically significant adverse reactions observed in both groups. CONCLUSION: The use of AN in patients with stage I-III primary knee OA was not inferior in efficacy to the combination of GC. Further studies with greater statistical power (sample size) and follow-up period are warranted including in real clinical practice.

Beauty from within: Oral administration of a sulfur-containing supplement methylsulfonylmethane improves signs of skin ageing.

Background: Methylsulfonylmethane (MSM) is an organosulfur compound with known benefits for joint health, sports nutrition, immune function, and anti-aging formulations and is gaining popularity as a nutritional supplement for the support of hair, skin and nails. Methods: The study was conducted in two steps; in Part I (pilot study) a panel of 20 participants ingested either 3 g a day of MSM or placebo capsules for 16 weeks. Visual and subject self assessment of wrinkles and skin texture as the predominant sign of ageing was observed. In Part II (dose-response study), 63 participants ingested either 1 g or 3 g per day of MSM for 16 weeks. Expert clinical grading, instrumental measurements and consumer perception was used to evaluate skin conditions like lines and wrinkles. Additionally, instrumentational analysis was conducted using corneometer and cutometer for investigation of skin hydration, firmness and elasticity. Results: Part I of the study clearly indicates that oral ingestion of MSM (3 g/d) reduces signs of ageing like facial wrinkles (p < 0.05) and skin roughness (p < 0.05) as compared to placebo. Detailed analysis in Part II instrumentation assessments showed a significant (p < 0.05) improvement from baseline in the severity of facial wrinkles, as well as improved skin firmness, elasticity and hydration with MSM. Some of these parameters exhibited a good dose-response indicating that the higher (3 g/d) of the supplement was more effective than the lower dose of 1 g/d, but generally the lower dose of 1 g/d appeared to be sufficiently effective in reducing the facial signs of ageing. Conclusion: This study indicated that MSM is effective in reducing visual signs of skin ageing even at a low dose of 1 g/d.

Methylsulfonylmethane sensitizes endometrial cancer cells to doxorubicin.

BACKGROUND: Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related disorders. It was also suggested that MSM might play a beneficial role in cancer treatment. PURPOSE: So far, the MSM might have a potentially beneficial effect in endometrial cancer (EC) treatment. STUDY DESIGN: This study evaluated the effect and usefulness of MSM in combinatory therapy with known drug doxorubicin (DOX). METHODS: The effect of combinational treatment of MSM and DOX on the induction of apoptosis was evaluated in EC cell lines (ISHIKAWA, MFE-296, MFE-280). RESULTS: We observed that MSM itself induces apoptosis in EC cell lines, and pre-treatment with MSM for 24 h increases the sensitivity of EC cells to DOX-induced apoptosis and DNA damage and that effect might be regulated by p42/44 (Erk1/2) MAPK and Akt (protein kinase B). CONCLUSION: These results for the first time show that MSM might act as a sensitizer of EC cells to known drugs, for which EC cells quickly acquire resistance. Graphical abstract.

Nutraceutical Approach to Chronic Osteoarthritis: From Molecular Research to Clinical Evidence.

Osteoarthritis (OA) is a degenerative inflammatory condition of the joint cartilage that currently affects approximately 58 million adults in the world. It is characterized by pain, stiffness, and a reduced range of motion with regard to the arthritic joints. These symptoms can cause in the long term a greater risk of overweight/obesity, diabetes mellitus, and falls and fractures. Although the current guidelines for the treatment of OA suggest, as the gold standard for this condition, pharmacological treatment characterized by non-steroidal anti-inflammatory drugs (NSAID), opioids, and cyclooxygenase (COX)-2-specific drugs, a great interest has been applied to nutraceutical supplements, which include a heterogeneous class of molecules with great potential to reduce inflammation, oxidative stress, pain, and joint stiffness and improve cartilage formation. The purpose of this review is to describe the potential application of nutraceuticals in OA, highlighting its molecular mechanisms of actions and data of efficacy and safety (when available).

MSM promotes human periodontal ligament stem cells differentiation to osteoblast and bone regeneration.

Periodontal disease is the most common chronic disease of the oral and maxillofacial region, causing alveolar bone loss and ultimate loss of tooth. The purpose of treatment of periodontal disease is to promote the regeneration of periodontal tissue, including alveolar bone, and implantation of fixtures to replace the missing tooth as a result of advanced periodontal disease also requires alveolar bone regeneration. Methylsulfonylmethane (MSM) is a sulfur compound with well-known anti-inflammatory effects but its effects on bone regeneration are unknown. In this study, we investigated the effects of MSM on osteogenic differentiation of human PDLSCs (hPDLSCs) in vitro and in vivo. Our results demonstrate that MSM not only promotes the proliferation but also promotes osteogenic differentiation of hPDLSCs. MSM increased the expression levels of osteogenic specific markers that ALP, OPN, OCN, Runx2, and OSX. Smad2/3 signaling pathway was reinforced by MSM. Runx2, which downstream of Smad pathway, was expressed in accordance. Consistent with in vitro results, in vivo calvarial defect model and transplantation model revealed that MSM induces hPDLSCs to differentiate into osteoblast, which express ALP, OPN and OCN highly and enhance bone formation. These results suggest that MSM promotes osteogenic differentiation and bone formation of hPDLSCs, and Smad2/3 / Runx2 / OSX / OPN may play critical roles in the MSM-induced osteogenic differentiation. Thus, MSM combined with hPDLSCs may be a good candidate for future clinical applications in alveolar bone regeneration and can be used for graft material in reconstructive dentistry.

Osteogenic Properties of Novel Methylsulfonylmethane-Coated Hydroxyapatite Scaffold.

Despite numerous advantages of using porous hydroxyapatite (HAp) scaffolds in bone regeneration, the material is limited in terms of osteoinduction. In this study, the porous scaffold made from nanosized HAp was coated with different concentrations of osteoinductive aqueous methylsulfonylmethane (MSM) solution (2.5, 5, 10, and 20%) and the corresponding MH scaffolds were referred to as MH2.5, MH5, MH10, and MH20, respectively. The results showed that all MH scaffolds resulted in burst release of MSM for up to 7 d. Cellular experiments were conducted using MC3T3-E1 preosteoblast cells, which showed no significant difference between the MH2.5 scaffold and the control with respect to the rate of cell proliferation (p > 0.05). There was no significant difference between each group at day 4 for alkaline phosphatase (ALP) activity, though the MH2.5 group showed higher level of activity than other groups at day 10. Calcium deposition, using alizarin red staining, showed that cell mineralization was significantly higher in the MH2.5 scaffold than that in the HAp scaffold (p < 0.0001). This study indicated that the MH2.5 scaffold has potential for both osteoinduction and osteoconduction in bone regeneration.

Safety and Molecular-Toxicological Implications of Cannabidiol-Rich Cannabis Extract and Methylsulfonylmethane Co-Administration.

Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we investigated the interaction potential between the cannabidiol-rich cannabis extract (CRCE) and methylsulfonylmethane (MSM), a popular dietary supplement, in the mouse model. For this purpose, 8-week-old male C57BL6/J mice received MSM-containing water (80 mg/100 mL) ad libitum for 17 days. During the last three days of treatment, mice received three doses of CRCE administered in sesame oil via oral gavage (123 mg/kg/day). Administration of MSM alone did not result in any evidence of liver toxicity and did not induce expression of mouse cytochrome P450 (CYP) enzymes. Administration of CRCE did produce significant (p < 0.05) increases in Cyp1a2, Cyp2b10, Cyp2c29, Cyp3a4, Cyp3a11, Cyp2c65, and Cyp2c66 messenger RNA, however, this effect was not amplified by MSM/CRCE co-treatment. Similarly, no evidence of liver toxicity was observed in MSM/CRCE dosed mice. In conclusion, short-term MSM/CRCE co-administration did not demonstrate any evidence of hepatotoxicity in the mouse model.

Conjugation with Methylsulfonylmethane Improves Hyaluronic Acid Anti-Inflammatory Activity in a Hydrogen Peroxide-Exposed Tenocyte Culture In Vitro Model.

Rotator cuff tears (RCTs) and rotator cuff disease (RCD) are important causes of disability in middle-aged individuals affected by nontraumatic shoulder dysfunctions. Our previous studies have demonstrated that four different hyaluronic acid preparations (HAPs), including Artrosulfur® hyaluronic acid (HA) (Alfakjn S.r.l., Garlasco, Italy), may exert a protective effect in human RCT-derived tendon cells undergoing oxidative stress damage. Recently, methylsulfonylmethane (MSM) (Barentz, Paderno Dugnano, Italy) has proven to have anti-inflammatory properties and to cause pain relief in patients affected by tendinopathies. This study aims at evaluating three preparations (Artrosulfur® HA, MSM, and Artrosulfur® MSM + HA) in the recovery from hydrogen peroxide-induced oxidative stress damage in human tenocyte. Cell proliferation, Lactate Dehydrogenase (LDH) release, and inducible nitric oxide synthases (iNOS) and prostaglandin E2 (PGE2) modulation were investigated. In parallel, expression of metalloproteinases 2 (MMP2) and 14 (MMP14) and collagen types I and III were also examined. Results demonstrate that Artrosulfur® MSM + HA improves cell escape from oxidative stress by decreasing cytotoxicity and by reducing iNOS and PGE2 secretion. Furthermore, it differentially modulates MMP2 and MMP14 levels and enhances collagen III expression after 24 h, proteins globally related to rapid acceleration of the extracellular matrix (ECM) remodelling and thus tendon healing. By improving the anti-cytotoxic effect of HA, the supplementation of MSM may represent a feasible strategy to ameliorate cuff tendinopathies.

Methylsulfonylmethane and boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: Randomized trial.

Until now glucosamine sulfate (GS) has been the most widely used supplement and has been shown to be efficacious in the treatment of osteoarthritis (OA). Methylsulfonylmethane (MSM) and boswellic acids (BA) are new effective supplements for the management of inflammation and joint degeneration, according to previous experimental studies. The aim of our study is to test the effectiveness of association of MSM and BA in comparison with GS in knee arthritis.In this prospective randomized clinical trial, MEBAGA (Methylsulfonylmethane and Boswellic Acids versus Glucosamine sulfate in the treatment of knee Arthritis), 120 participants affected by arthritis of the knee were randomly assigned to an experimental group (MB group) or a control group (GS group) treated for 60 days with 5 g of MSM and 7.2 mg of BA or with 1500 mg of GS daily, respectively. At the 2-month (T1) and 6-months (T2) follow-up , the efficacy of these two nutraceuticals was assessed using the visual analog pain scale (VAS) and the Lequesne Index (LI) for joint function, along with the use of anti-inflammatory drugs (non-steroidal anti-inflammatory drugs and anti-cyclooxygenase-2).The repeated measures ANOVA analysis shows that for VAS, LI, and the use of anti-inflammatory drugs scores there are improvements due to the time in the two groups (respectively, F=26.0; P<0.0001; F=4.15; P=0.02; F=3.38; P=0.04), with a tendency to better values for the MB group at T2.On the basis of these preliminary data, we could support the efficacy of the MSM in association with BA in the treatment of OA. These results are consistent with the anti-inflammatory and chondroprotective effects previously occurred in experimental studies. This new combination of integration (MSM and BS) has presented good results and satisfactory in comparison with GS, until now the cornerstone of the treatment of arthritis in according to guidelines.

Metabolic fingerprint of dimethyl sulfone (DMSO2) in microbial-mammalian co-metabolism.

There is growing awareness that intestinal microbiota alters the energy harvesting capacity of the host and regulates metabolism. It has been postulated that intestinal microbiota are able to degrade unabsorbed dietary components and transform xenobiotic compounds. The resulting microbial metabolites derived from the gastrointestinal tract can potentially enter the circulation system, which, in turn, affects host metabolism. Yet, the metabolic capacity of intestinal microbiota and its interaction with mammalian metabolism remains largely unexplored. Here, we review a metabolic pathway that integrates the microbial catabolism of methionine with mammalian metabolism of methanethiol (MT), dimethyl sulfide (DMS), and dimethyl sulfoxide (DMSO), which together provide evidence that supports the microbial origin of dimethyl sulfone (DMSO2) in the human metabolome. Understanding the pathway of DMSO2 co-metabolism expends our knowledge of microbial-derived metabolites and motivates future metabolomics-based studies on ascertaining the metabolic consequences of intestinal microbiota on human health, including detoxification processes and sulfur xenobiotic metabolism.

Methylsulfonylmethane modulates apoptosis of LPS/IFN-γ-activated RAW 264.7 macrophage-like cells by targeting p53, Bax, Bcl-2, cytochrome c and PARP proteins.

Methylsulfonylmethane (MSM) is a non-toxic, natural organosulfur compound, which is known to possess antioxidant and anti-inflammatory activities. In recent years, MSM has been widely used as a dietary supplement for its beneficial effects against various diseases, especially arthritis. Despite being a popular supplement product, the mechanism of action of MSM is not well known. This study was designed to investigate the effects of MSM on cytotoxic signals induced by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) in RAW 264.7 macrophage-like cells. The results showed that MSM reversed apoptosis of RAW 264.7 macrophage-like cells at non-cytotoxic concentrations probably through the modulation of apoptotic proteins. After pre-treatment of cells with non-toxic doses of MSM; caspase-3 activation, p53 accumulation, cytochrome c release and Bax/Bcl-2 ratio were significantly decreased and full length poly ADP-ribose polymerase (PARP) was significantly increased. In addition, the loss of mitochondrial membrane potential was decreased with MSM pretreatment in activated macrophages. Since excess nitric oxide production causes apoptosis of macrophages, anti-apoptotic effects of MSM are thought to be mediated by its inhibitor effects on inducible nitric oxide synthase (iNOS) protein and nitric oxide levels. More interestingly, higher doses of MSM exhibited biphasic effects, inhibited cell viability, induced apoptosis of macrophages, increased caspase-3 activity and PARP cleavage. Thus, our results reveal the molecular mechanism of of MSM indicating that MSM supplementation may be beneficial for complications related to nitric oxide-dependent apoptosis in inflammatory conditions. However, the optimum concentration of MSM must be chosen carefully to elicit the desired effect.

Methylsulfonylmethane induces caspase-dependent apoptosis in acute myeloid leukemia cell lines.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous ailment in both biological and clinical concepts. Numerous efforts have been devoted to discover natural compounds for combating cancer, which showed great potential in cancer management. Methylsulfonylmethane (MSM), an organosulfur dietary supplement, is utilized for improving various clinical conditions, particularly osteoarthritis. MSM can exert antitumor activity in a wide range of cancers. OBJECTIVES: The molecular mechanisms of action underlying antileukemic activity of MSM remain unclear. In this regard, we aimed to investigate the anticancer properties of MSM on human AML cell lines (U937 and HL60) with focus on underlying cell death mechanism. METHODS: Anticancer activity of the MSM was examined employing MTT assay, Annexin V-PE/7AAD staining, caspase3/7 activity test, and real-time qPCR. Both cell lines were treated with different concentrations (50-400 mM) of MSM for 24 h. Pretreatment of the cells with a caspase inhibitor (i.e., Z-VAD-fmk) was performed for the assessment of apoptosis induction. RESULTS: The results of MTT assay revealed that in both cell lines, the MSM markedly reduced cell viability in comparison to the control cells. Additionally, findings of Annexin V-7AAD staining revealed that MSM induced apoptosis and activated caspase 3/7 in both cell lines markedly. Real-time quantitative PCR results also supported the induction of apoptosis in AML cells. MSM altered the expression levels of various apoptotic genes (BAX, BAD, and BIM). CONCLUSION: Overall, our results indicated that MSM could induce apoptosis in AML cell lines in a dose-dependent manner, which therefore could be utilized as an antileukemic agent.

Efficacy and safety of an oral complementary medicine combination in people with symptomatic knee osteoarthritis: Protocol for the double-blind, randomized, placebo-controlled ATLAS trial.

Objective: To investigate the efficacy and safety of an oral complementary medicine combination formulation relative to placebo, on changes in pain intensity from baseline to week 12, in people with knee osteoarthritis (OA). Design: A placebo-controlled, double-blind, two-arm, superiority, phase II, Randomized Controlled Trial (RCT) (ACTRN12623000380695). We will recruit 82 participants (∼41 per arm), aged ≥40 years, with a clinical diagnosis of symptomatic knee OA and radiographic change on x-ray (Kellgren-Lawrence Grade ≥2). Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin® Super, 250 â€‹mg/day), pine bark extract (Fenoprolic™ 70 Organic 100 â€‹mg/day), curcumin (500 â€‹mg/day), piperine (5 â€‹mg/day), and methylsulfonylmethane (MSM, 1500 â€‹mg/day), or placebo, for 12-weeks. The primary endpoint will be change from baseline in average knee pain intensity at 12-weeks (visual analogue scale). Secondary endpoints will include change in knee pain from baseline to 12-weeks in the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, and health-related quality of life (AQoL-8D). Ethics and dissemination: This protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). Dissemination will occur through lay summaries, infographics, conference abstracts, oral presentations, theses, and scientific publications. Conclusion: This RCT will provide credible evidence about the efficacy and safety of this complementary medicine combination and inform updates to international clinical practice standards on the use of complementary medicines in the management of symptomatic knee OA.

Methylsulfonylmethane Improves Knee Quality of Life in Participants with Mild Knee Pain: A Randomized, Double-Blind, Placebo-Controlled Trial.

Methylsulfonylmethane (MSM) is a food ingredient present in small amounts in many foods, and its anti-inflammatory effects have been reported. We conducted a randomized, double-blind, placebo-controlled trial of oral consumption of MSM on mild pain of the knee joint in healthy Japanese participants. A total of 88 participants were enrolled in this study and randomly assigned to MSM consumption (n = 44) and placebo control (n = 44) groups. Both groups of participants took 10 tablets, each containing 200 mg MSM or lactose, per day for 12 weeks. The primary outcome of this study was measured values of the total score of the Japanese Knee Osteoarthritis Measure (JKOM) at 12 weeks after the test sample consumption. Safety evaluation was performed through physical examination, urine analysis, peripheral blood test, and medical interview. The total scores at 12 weeks in the MSM and placebo groups as the primary outcome were significantly different (p = 0.046). The health condition of JKOM also improved after MSM consumption (p = 0.032). The questionnaire results also suggested improvement in the knee and systemic health. This study indicated that MSM oral consumption improved both knee and systemic health conditions in healthy participants who experienced mild pain in the knee joint.

Methylsulfonylmethane Serves as a Donor of Methyl Groups for Methylation of DNA in Human Liver HepaRG Cells.

Methylsulfonylmethane (MSM), a natural organosulfur compound, is a popular dietary supplement sold both as a single product and as a constituent of multi-ingredient products. It has been postulated that MSM may serve as a donor for methyl groups for various cellular processes; however, studies have yet to demonstrate this. Therefore, the goal of this study was to determine whether or not MSM, supplemented to fully differentiated human HepaRG cells at physiologically-relevant concentrations, can serve as a donor for methyl groups for DNA methylation. For this purpose, methyl groups in the MSM molecule were labeled with deuterium (deuterated) and incorporation of the labeled 5-methylcytosine into the HepaRG cell DNA was evaluated using liquid chromatography/mass spectrometry (LC-MS/MS). We report that MSM supplementation resulted in significant incorporation of deuterated product into DNA in a time- and dose-dependent fashion. These changes were not associated with increased 5-methylcytosine content, did not result in changes of DNA methylation or re-distribution of DNA methylation patterns between the retrotransposons LINE-1 and HERV18, and were not associated with cytotoxicity. In conclusion, short-term supplementation with MSM in vitro demonstrates that MSM can serve as a donor of methyl groups for methylation of DNA, but does not affect the levels of DNA methylation globally and does not lead to redistribution of the DNA methylation patterns within the most abundant repetitive elements. Future studies will be needed to validate these findings in vivo and to investigate whether or not MSM can restore normal DNA methylation patterns within the hypomethylated phenotype.

Methylsulfonylmethane ameliorates metabolic-associated fatty liver disease by restoring autophagy flux via AMPK/mTOR/ULK1 signaling pathway.

Introduction: Metabolism-associated fatty liver disease (MAFLD) is a global health concern because of its association with obesity, insulin resistance, and other metabolic abnormalities. Methylsulfonylmethane (MSM), an organic sulfur compound found in various plants and animals, exerts antioxidant and anti-inflammatory effects. Here, we aimed to assess the anti-obesity activity and autophagy-related mechanisms of Methylsulfonylmethane. Method: Human hepatoma (HepG2) cells treated with palmitic acid (PA) were used to examine the effects of MSM on autophagic clearance. To evaluate the anti-obesity effect of MSM, male C57/BL6 mice were fed a high-fat diet (HFD; 60% calories) and administered an oral dose of MSM (200 or 400 mg/kg/day). Moreover, we investigated the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin complex 1 (mTORC1)/UNC-51-like autophagy-activating kinase 1 (ULK1) signaling pathway to further determine the underlying action mechanism of MSM. Results: Methylsulfonylmethane treatment significantly mitigated PA-induced protein aggregation in human hepatoma HepG2 cells. Additionally, Methylsulfonylmethane treatment reversed the PA-induced impairment of autophagic flux. Methylsulfonylmethane also enhanced the insulin sensitivity and significantly suppressed the HFD-induced obesity and hepatic steatosis in mice. Western blotting revealed that Methylsulfonylmethane improved ubiquitinated protein clearance in HFD-induced fatty liver. Remarkably, Methylsulfonylmethane promoted the activation of AMPK and ULK1 and inhibited mTOR activity. Conclusion: Our study suggests that MSM ameliorates hepatic steatosis by enhancing the autophagic flux via an AMPK/mTOR/ULK1-dependent signaling pathway. These findings highlight the therapeutic potential of MSM for obesity-related MAFLD treatment.

Rationally Designed Eco-Friendly Solvent System for High-Performance, Large-Area Perovskite Solar Cells and Modules.

The important but remained issue to be addressed to achieve the mass production of perovskite solar modules include a large-area fabrication of high-quality perovskite film with eco-friendly, viable production methods. Although several efforts are made to achieve large-area fabrication of perovskite, the development of eco-friendly solvent system, which is precisely designed to be fit to scale-up methods are still challenging. Herein, this work develops the eco-friendly solvent/co-solvent system to produce a high-quality perovskite layer with a bathing in eco-friendly antisolvent. The new co-solvent/additive, methylsulfonylmethane (MSM), efficiently improves the overall solubility and has a suitable binding strength to the perovskite precursor, resulting in a high-quality perovskite film with antisolvent bathing method in large area. The resultant perovskite solar cells showed high power conversion efficiency of over 24% (in reverse scan), with a good long-term stability under continuous light illumination or damp-heat condition. MSM is also beneficial to produce a perovskite layer at low-temperature or high-humidity. MSM-based solvent system is finally applied to large-area, resulting in highly efficiency perovskite solar modules with PCE of 19.9% (by aperture) or 21.2% (by active area) in reverse scan. These findings contribute to step forward to a mass production of perovskite solar modules with eco-friendly way.

Effects of Methylsulfonylmethane on UVB-induced Skin Damage: An Experimental Study in a Mouse Model.

BACKGROUND/AIM: The skin protects the body from ultraviolet rays and other external factors. Various studies have been conducted to identify methods to prevent skin aging and damage. To investigate the protective effects of methylsulfonylmethane (MSM), in this study, a hairless mouse model was used. PATIENTS AND METHODS: Mice divided into Groups B, C, and D were subjected to UVB irradiation for six weeks, and Group A was considered the control. Retinoic acid is a substance that has been proven to have anti-aging properties. Group C was injected with MSM, group D was injected with retinoic acid, and groups A and B were injected with saline. At the end of the experiment, the degree of senescence was confirmed through visual evaluation, histopathological analysis, immunohistochemistry, and elasticity measurement using SEM. RESULTS: After the end of the experiment, the wrinkle score was 0.4, 2.5, 1.8, 1.5 for Groups A, B, C, and D, respectively. Epidermal thickness was 40 µm, 70 µm, 60 µm, 55 µm in Groups A, B, C, and D, respectively. Group C showed less collagen confirmation loss and more angiogenesis and elastin precursor production. Elastic fiber linearity was 0.901±0.02, 0.551±0.04, 0.751±0.04, 0.822±0.03 for Groups A, B, C, and D, respectively. CONCLUSION: Injection of MSM in mice subjected to UVB-induced skin damage reduces the wrinkle score and protects against photoaging.