Protective effects of arbutin against doxorubicin-induced cardiac damage.

BACKGROUND: Doxorubicin is an effective antineoplastic agent but has limited clinical application because of its cumulative toxicities, including cardiotoxicity. Cardiotoxicity causes lipid peroxidation, genetic impairment, oxidative stress, inhibition of autophagy, and disruption of calcium homeostasis. Doxorubicin-induced cardiotoxicity is frequently tried to be mitigated by phytochemicals, which are derived from plants and possess antioxidant, anti-inflammatory, and anti-apoptotic properties. Arbutin, a natural antioxidant found in the leaves of the bearberry plant, has numerous pharmacological benefits, including antioxidant, anti-bacterial, anti-hyperglycemic, anti-inflammatory, and anti-tumor activity. METHODS AND RESULTS: The study involved male Wistar rats divided into three groups: a control group, a group treated with doxorubicin (20 mg/kg) to induce cardiac toxicity, a group treated with arbutin (100 mg/kg) daily for two weeks before doxorubicin administration. After treatment, plasma and heart tissue samples were collected for analysis. The samples were evaluated for oxidative stress parameters, including superoxide dismutase, malondialdehyde, and catalase, as well as for cardiac biomarkers, including CK, CK-MB, and LDH. The heart tissues were also analyzed using molecular (TNF-α, IL-1ß and Caspase 3), histopathological and immunohistochemical methods (8-OHDG, 4 Hydroxynonenal, and dityrosine). The results showed that arbutin treatment was protective against doxorubicin-induced oxidative damage by increasing SOD and CAT activity and decreasing MDA level. Arbutin treatment was similarly able to reverse the inflammatory response caused by doxorubicin by reducing TNF-α and IL-1ß levels and also reverse the apoptosis by decreasing caspase-3 levels. It was able to prevent doxorubicin-induced cardiac damage by reducing cardiac biomarkers CK, CK-MB and LDH levels. In addition to all these results, histopathological analyzes also show that arbutin may be beneficial against the damage caused by doxorubicin on heart tissue. CONCLUSION: The study suggests that arbutin has the potential to be used to mitigate doxorubicin-induced cardiotoxicity in cancer patients.

Arbutin: Occurrence in Plants, and Its Potential as an Anticancer Agent.

Arbutin, a hydroquinone glucoside, has been detected in ca. 50 plant families, especially in the plants of the Asteraceae, Ericaceae, Proteaceae and Rosaceae families. It is one of the most widely used natural skin-whitening agents. In addition to its skin whitening property, arbutin possesses other therapeutically relevant biological properties, e.g., antioxidant, antimicrobial and anti-inflammatory, as well as anticancer potential. This review presents, for the first time, a comprehensive overview of the distribution of arbutin in the plant kingdom and critically appraises its therapeutic potential as an anticancer agent based on the literature published until the end of August 2022, accessed via several databases, e.g., Web of Science, Science Direct, Dictionary of Natural Products, PubMed and Google Scholar. The keywords used in the search were arbutin, cancer, anticancer, distribution and hydroquinone. Published outputs suggest that arbutin has potential anticancer properties against bladder, bone, brain, breast, cervix, colon, liver, prostate and skin cancers and a low level of acute or chronic toxicity.

Effects of Itxasol© Components on Gene Expression in Bacteria Related to Infections of the Urinary Tract and to the Inflammation Process.

Urinary tract infections (UTIs) represent a health problem of the first magnitude since they affect large segments of the population, cause increased mortality and comorbidity, and have a high incidence of relapse. Therefore, UTIs cause a major socioeconomic concern. Current antibiotic treatments have various limitations such as the appearance of resistance to antibiotics, nephrotoxicity, and side effects such as gastrointestinal problems including microbiota alterations that contribute to increasing antibiotic resistance. In this context, Itxasol© has emerged, approved as an adjuvant for the treatment of UTIs. Designed with biomimetic principles, it is composed of arbutin, umbelliferon, and N-acetyl cysteine. In this work, we review the activities of these three compounds concerning the changes they produce in the expression of bacterial genes and those related to inflammation as well as assess how they are capable of affecting the DNA of bacteria and fungi.

A Natural Alternative Treatment for Urinary Tract Infections: Itxasol©, the Importance of the Formulation.

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.

Natural Cosmeceutical Ingredients for Hyperpigmentation.

As Dermatologists caring for patients with hyperpigmentation problems, we are always looking for more alternative therapies. Hydroquinone (HQ) is still the standard of care. However, traditional depigmenting agents such as HQ and corticosteroids, although highly effective, can raise safety concerns including exogenous ochronosis, atrophy, carcinogenesis and local and systemic untoward effects with long term use. Therefore, we need to investigate non-prescription natural alternatives. This manuscript presents many of the natural ingredients found in cosmeceuticals for the treatment of hyperpigmentation and their mechanisms of action. It will also describe the melanocyte activation pathways and how each of these ingredients interferes with it.

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®).

BACKGROUND: Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. METHODS: 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. RESULTS: Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. CONCLUSIONS: Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. TRIAL REGISTRATION: NCT02130713. Date of trial Registration: 30/04/2014.

Investigation of Possible Positive Effects of Arbutin Application in Experimental Colitis Model.

BACKGROUND/AIMS:  This study aimed to investigate the possible positive effects of arbutin in a trinitrobenzene sulfonic acid (TNBS)- induced experimental colitis model, to compare it with mesalazine, which is used in treating inflammatory bowel disease and to observe the effect of its concomitant use. MATERIALS AND METHODS:  Forty Wistar albino species male rats were randomized into 5 groups as control, colitis, colitis+arbutin (Arb), colitis+mesalazine (Mes), and colitis+mesalazine+arbutin (M+A). Proinflammatory cytokines [interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha (TNF-α)] and oxidant/antioxidant parameters [malondialdehyde (MDA), superoxide dismutase inhibition (SOD) inhibition, myeloperoxidase (MPO), and catalase, glutathione peroxidase (GPx)] were processed from the samples. Histopathological evaluation evaluated goblet cell reduction, cellular infiltration, and mucosal loss. RESULTS:  When the treatment groups and the TNBS group were compared, statistical significance was achieved in MDA, MPO, SOD inhibition, GPx values, IL-6, IL-1ß and TNF-α levels. Histopathological evaluation revealed a statistically significant decrease in the mucosal loss value in the group where mesalazine and arbutin were used together compared to the TNBS group. CONCLUSION:  Our study's results elaborated that using arbutin alone or in combination with mesalazine produced positive effects in colitis-induced rats.

[Arbutin ameliorates liver fibrosis in mice by inhibiting macrophage recruitment and regulating the Akt/NF-κB and Smad signaling pathways].

OBJECTIVE: To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. METHODS: Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low- and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutintreated LX-2 cells were detected with Western blotting. RESULTS: Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P < 0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of a-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a mRNA levels in mice (P < 0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. CONCLUSION: Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.

Pharmacological and biochemical insights into lead-induced hepatotoxicity: Pathway interplay and the protective effects of arbutin via the oral and intraperitoneal routes in silico and in vivo.

INTRODUCTION: Lead acetate (PbAc), a hazardous heavy metal, poses significant threats to human health and the environment because of widespread industrial exposure. PbAc exposure leads to liver injury primarily through oxidative stress and the disruption of key regulatory pathways. Understanding these mechanisms and exploring protective agents are vital for mitigating PbAc-induced hepatotoxicity. Therefore, we aimed to investigate the molecular pathways implicated in PbAc-induced liver damage, focusing on Sirt-1, Nrf2 (HO-1, NQO1, and SOD), Akt-1/GSK3ß, m-TOR, and P53. Additionally, we aimed to assess the hepatoprotective effects of arbutin, which is administered orally and intraperitoneally, to determine the most effective delivery method. METHODOLOGY: In silico analyses were conducted to identify relevant protein networks associated with Sirt-1 and AKT-1/GSK-3B pathways. The pharmacodynamic properties of arbutin were examined, followed by molecular docking studies to elucidate its interactions with the selected protein network. In vivo preclinical studies were carried out on adult male rats randomly assigned to 6 different treatment groups, including PbAc exposure and PbAc exposure treated with arbutin either orally or intraperitoneally. RESULTS: PbAc exposure led to hepatic oxidative stress, as evidenced by elevated MDA levels and SIRT-1 inhibition, disrupting antioxidant pathways and activating antiautophagic and proapoptotic pathways, ultimately resulting in hepatocyte necrosis. Both oral and intraperitoneal arbutin administration effectively modifed these effects, with intraperitoneal delivery showing superior efficacy in mitigating PbAc-induced histological, immunological, and biochemical alterations. CONCLUSION: This study provides insights into the molecular mechanisms underlying PbAc-induced liver injury and highlights the hepatoprotective potential of arbutin. These findings suggest that arbutin, particularly when administered intraperitoneally, holds promise as a therapeutic agent for combating PbAc-induced hepatotoxicity.

4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation.

BACKGROUND: Hyperpigmentary disorders like melasma, actinic and senile lentigines are a major cosmetic concern. Therefore, many topical products are available, containing various active ingredients aiming to reduce melanin production and distribution. The most prominent target for inhibitors of hyperpigmentation is tyrosinase, the key regulator of melanin production. Many inhibitors of tyrosinase are described in the literature; however, most of them lack clinical efficacy. METHODS: We were interested in evaluating the inhibition of skin pigmentation by well-known compounds with skin-whitening activity like hydroquinone, arbutin, kojic acid and 4-n-butylresorcinol. We compared the inhibition of human tyrosinase activity in a biochemical assay as well as inhibition of melanin production in MelanoDerm skin model culture. For some compounds, the in vivo efficacy was tested in clinical studies. RESULTS: Arbutin and hydroquinone only weakly inhibit human tyrosinase with a half maximal inhibitory concentration (IC(50)) in the millimolar range. Kojic acid is 10 times more potent with an IC(50) of approximately 500 µmol/L. However, by far the most potent inhibitor of human tyrosinase is 4-n-butylresorcinol with an IC(50) of 21 µmol/L. In artificial skin models, arbutin was least active with an IC(50) for inhibition of melanin production > 5000 µmol/L. Kojic acid inhibited with an IC(50) > 400 µmol/L. Interestingly, hydroquinone inhibited melanin production in MelanoDerms with an IC(50) below 40 µmol/L, probably due to a mechanism different from tyrosinase inhibition. Again, 4-n-butylresorcinol was the most potent inhibitor with an IC(50) of 13.5 µmol/L. In vivo efficacy of 4-n-butyl-resorcinol was confirmed in clinical studies. Subjects with age spots on the forearm treated twice daily two age spots with a formula containing 4-n-butylresorcinol and two control age spots with the corresponding vehicle. Within 8 weeks, 4-n-butylresorcinol reduced visibly the appearance of age spots, while the control spots showed no improvement. A second study showed that 4-butylresorcinol was more effective than 4-hexylresorcinol and 4-phenylethylresorcinol. CONCLUSION: The present in vitro and in vivo data prove the high inhibitory capacity of 4-n-butylresorcinol on human tyrosinase activity, exceeding by far the potency of hydroquinone, arbutin and kojic acid. The resulting clinical improvement of skin hyperpigmentations reveals 4-n-butylresorcinol as a very valuable active compound for the management of pigmentation disorders.

Effect of plant polyphenols on ischemia-reperfusion injury of the isolated rat heart and vessels.

In the present study, we investigated the potential protective effect of selected natural substances in a rat model of heart and mesenteric ischemia-reperfusion (I/R). Experiments were performed on isolated Langendorff-perfused rat hearts, subjected to 30-min global ischemia, followed by 30-min reperfusion. Arbutin, curcumin, rosmarinic acid and extract of Mentha x villosa were applied in the concentration of 1 × 10⁻5 mol/l 10 min before the onset of ischemia and during reperfusion, through the perfusion medium. Mesenteric ischemia was induced by clamping the superior mesenteric artery (SMA) for 60 min, subsequent reperfusion lasted 30 min. Production of reactive oxygen species (ROS) by SMA ex vivo was determined by luminol-enhanced chemiluminiscence (CL). The effect of the substances was tested after their incubation with tissue. Curcumin and extract of Mentha x villosa were found to be the most effective in reducing reperfusion-induced dysrhythmias--ventricular tachycardia and fibrillation. This effect was accompanied by bradycardic effect. The mesenteric I/R induced an increase in CL in vascular tissue which was dampened by substances tested. All substances tested were found to have antioxidant properties, as demonstrated by a reduction in ROS production in mesenteric vessels. This effect was confirmed in curcumin and extract of Mentha x villosa which reduced reperfusion dyshythmias.

Evaluation of the therapeutic effects of arbutin on cisplatin-induced ovarian toxicity in rats through endoplasmic reticulum stress and Nrf2 pathway.

Arbutin (ARB) is a glycosylated hydroquinone with potent antioxidant effects. Although cisplatin (CP) is widely used in chemotherapy, its toxicity in healthy tissues, including ovotoxicity, is an insurmountable problem. This study aimed to evaluate the therapeutic effect of ARB against CP-related ovototoxicity by including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rats for the first time. Rats treated one dose of CP (5 mg/kg) on the first day, followed by ARB (5 and 10 mg/kg) for three days. Serum reproductive hormone levels were determined using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in ovarian tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of ARB on this situation were also addressed. ARB treatment reduced the levels of markers of OS, inflammation, ERS and apoptosis in ovarian tissue of CP-stimulated animals. ARB regenerated the depleted antioxidant system by triggering Nrf2 pathway in the ovarian tissues of animals stimulated by CP. Histological findings also supported the therapeutic efficacy of ARB. The results indicate that ARB may have therapeutic effects against CP-induced reproductive toxicity with its Nrf2 activator potential. ARB should be tested in more extensive studies as a new generation chemopreventive candidate molecule.

Arbutin ameliorates hyperglycemia, dyslipidemia and oxidative stress and modulates adipocytokines and PPARγ in high-fat diet/streptozotocin-induced diabetic rats.

Arbutin is a glycosylated hydroquinone with antioxidant and anti-hyperglycemia effects. However, its beneficial effects in type 2 diabetes (T2D) were not clarified. This study evaluated the effect of arbutin on hyperglycemia, dyslipidemia, insulin resistance, oxidative stress, and inflammatory response in T2D. Rats induced by high fat diet and streptozotocin were treated with arbutin (25 and 50 mg/kg) for 4 weeks. Diabetic rats exhibited glucose intolerance, elevated HbA1c%, reduced insulin, and high HOMA-IR. Liver glycogen and hexokinase activity were decreased in T2D rats while glucose-6-phosphatase (G6Pase), fructose-1,6- biphosphatase (FBPase), and glycogen phosphorylase were upregulated. Circulating and hepatic cholesterol and triglycerides and serum transaminases were elevated in T2D rats. Arbutin ameliorated hyperglycemia, dyslipidemia, insulin deficiency and resistance, and liver glycogen and alleviated the activity of carbohydrate-metabolizing enzymes. Both doses of arbutin decreased serum transaminases and resistin, and liver lipids, TNF-α, IL-6, malondialdehyde and nitric oxide, downregulated liver resistin and fatty acid synthase, and increased serum and liver adiponectin, and liver reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). These effects were associated with the upregulation of hepatic PPARγ. Arbutin inhibited α-glucosidase in vitro and in silico investigations revealed the ability of arbutin to bind PPARγ, hexokinase, and α-glucosidase. In conclusion, arbutin effectively ameliorated glucose intolerance, insulin resistance, dyslipidemia, inflammation, and oxidative stress, and modulated carbohydrate-metabolizing enzymes, antioxidants, adipokines and PPARγ in T2D in rats.

Topical treatment of hyperpigmentation disorders.

Hyperpigmentation has traditionally been a relatively difficult condition to treat, especially in darker racial ethnic groups. Multiple topical agents available act upon different steps of the pigmentation pathway. We review these topical agents, their mechanisms of action, and their effectiveness as monotherapy and in combination with other compounds. Ultimately, combination therapy is the most efficacious when considering overall depigmentation as well as treatment time required to achieve clinical improvement.

Natural options for the management of hyperpigmentation.

Facial hyperpigmented disorders are a common complaint in the adult population of all races. First-line topical treatments are usually hydroquinone or topical retinoids, which can cause irritant reactions. The need for better tolerated, yet effective, skin lightening agents that could be utilized by a wider population has led to the investigation of several potential botanical/natural compounds. There are currently many topical cosmetic formulations claiming skin depigmenting effects. A few of the ingredients (e.g. soy) are supported not only by in vitro results but also by a body of controlled clinical efficacy studies; other ingredients, instead, are backed mostly by in vitro data and a few small uncontrolled clinical studies. In this review, we describe the most common natural ingredients used for skin depigmentation and their major published studies: soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, COFFEEBERRY(™) and green tea.

Arbutin ameliorates glucocorticoid-induced osteoporosis through activating autophagy in osteoblasts.

Chronic long-term glucocorticoid use causes osteoporosis partly by interrupting osteoblast homeostasis and exacerbating bone loss. Arbutin, a natural hydroquinone glycoside, has been reported to have biological activities related to the differentiation of osteoblasts and osteoclasts. However, the role and underlying mechanism of arbutin in glucocorticoid-induced osteoporosis are elusive. In this study, we demonstrated that arbutin administration ameliorated osteoporotic disorders in glucocorticoid dexamethasone (Dex)-induced mouse model, including attenuating the loss of bone mass and trabecular microstructure, promoting bone formation, suppressing bone resorption, and activating autophagy in bone tissues. Furthermore, Dex-stimulated mouse osteoblastic MC3T3-E1 cells were treated with arbutin. Arbutin treatment rescued Dex-induced repression of osteoblast differentiation and mineralization, the downregulation of osteogenic gene expression, reduced autophagic marker expression, and decreased autophagic puncta formation. The application of autophagy inhibitor 3-MA decreased autophagy, differentiation, and mineralization of MC3T3-E1 cells triggered by arbutin. Taken together, our findings suggest that arbutin treatment fends off glucocorticoid-induced osteoporosis, partly through promoting differentiation and mineralization of osteoblasts by autophagy activation.

Arbutin ameliorated ulcerative colitis of mice induced by dextran sodium sulfate (DSS).

Accumulating evidence has revealed the anti-inflammatory effects of arbutin against various diseases. However, the effects of arbutin are not clarified in ulcerative colitis. This study was intended to investigate the protective effects and mechanisms of arbutin on DSS-induced colitis. Hematoxylin eosin staining was performed to determine the pathological damage of intestinal tissue in mice. Inflammatory factors levels in intestinal tissue were detected by enzyme linked immunosorbent assay (ELISA) assay. TUNEL staining showed the apoptosis levels of cells. Intestinal permeability was analyzed using the application of Fluorescein isothiocyanate Dextran (FD) 4. The levels of Zona Occludens 1 (ZO-1), occluding and claudin-1, and the related proteins in MAPK/ELK1 pathway were analyzed by Western blot. DSS promotes pathological injury, the levels of pro-inflammatory factors containing tumor necrosis factor alpha (TNF-α), Interleukin- 6 (IL-6) and myeloperoxidase (MPO), and cell apoptosis in the mouse colon. Additionally, intestinal permeability was increased and the levels of tight function-related proteins were increased following DSS induction. Its effects could be greatly improved by arbutin. Arbutin exerted effects by eliciting anti-inflammatory effects and maintaining normal intestinal mucosal barrier function, the action mechanism of which could be associated with MAPK/ELK1 pathway.

Fatty acid synthase inhibition ameliorates diabetes induced liver injury in rodent experimental model.

The abnormal dietary life style leads to hyperlipidemia and insulin resistance with ectopic lipid accumulation and elevated levels of hepatic glucose development which are the underlying pathological characteristics of fatty liver diseases. The pharmacological inhibition of fatty acid synthase of de novo lipogenesis may regulate the dysfunctional lipid biotransformation and reverse the pathological state of diabetic liver injury. The three pharmacological interventions (PTS; Pterostilbene, ARB; Arbutin, PUR; Purpurin) were administered to manage the condition of diabetic liver injury against the high fat diet (HFD) + Streptozotocin (STZ) 30 mg/kg b.wt. rodent animal model to observe the effect of abnormal fatty acid synthesis. The qRT-PCR was used to evaluate the fatty acid synthase (FASN) expression which is independently allied with diabetes associated fatty liver disorders. To determine the therapeutic potential of three selected drugs, the biochemical parameters and histopathological considerations were utilized. Three subsequent dosage of PTS, ARB and PUR administered (i.e., 30,60 & 120 mg/kg/p.o.) for five weeks significantly alter the serum parameters, oxidative burden in HFD-STZ which, in turn, resulted in diabetic liver injury. It was also revealed that increased mRNA expression of fatty acid synthase (FASN), which is known to promote abnormal fatty acid synthesis through different molecular signaling pathways, was associated with the development of diabetes associated liver injury, this expression was observed to be significantly suppressed by PTS, ARB and PUR treatment. Moreover, the studies of histopathology showed that there was substantial structural improvement after PTS, ARB and PUR treatment. All three selected drugs have been shown to be effective for Diabetic liver injury (DLI) care but PTS shows impressive results compared to other selected drugs.

Arbutin suppresses osteosarcoma progression via miR-338-3p/MTHFD1L and inactivation of the AKT/mTOR pathway.

Arbutin, a glycoside extracted from the plant Arctostaphylos uva-ursi, has been previously reported to possess antioxidant, anti-inflammatory and anticancer effects. Here, we investigated whether arbutin affects the proliferation of the cells of the osteosarcoma (OS) cell lines MG-63 and SW1353. Arbutin suppressed OS cell viability in a dose- and time-dependent manner, as shown by Cell Counting Kit-8 assay. Furthermore, arbutin exposure decreased the protein levels of MTHFD1L, CCND1 and phosphorylated-protein kinase B (AKT)/phosphorylated-mammalian target of rapamycin (mTOR). Potential upstream miRNAs of MTHFD1L were predicted using TargetScan, PICTAR5, miRanda and miRWalk. We performed luciferase activity assays to show that miR-338-3p directly targets and negatively regulates the expression of MTHFD1L. Knockdown of miR-338-3p promoted cell invasion, migration and proliferation in arbutin-treated OS cells via MTHFD1L. In summary, our data suggest that arbutin inhibits OS cell proliferation, migration and invasion via miR-338-3p/MTHFD1L and by inactivating the AKT/mTOR pathway.

Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: a prospective study.

OBJECTIVE: To evaluate the effectiveness of a Q-switched Nd:YAG laser (MedLite C6; HOYA ConBio, Fremont, CA, USA) and 7% alpha arbutin solution (Skin Advance Laboratory, Japan) in the treatment of melasma. METHODS: This was a prospective study of 35 refractory melasma cases treated with 10 weekly laser sessions, two monthly follow-up treatments and topical 7% alpha arbutin solution. Clinical photographs and severity grading on a 5-point scale were carried out by an independent observer at each visit. RESULTS: At 6 months, 30% of study subjects received results in the excellent clearance category (> 81% reduction of melasma) and 36.7% received good (51-80% reduction) clearance. Mild and transient side effects included discomfort during treatment, erythema, whitening of fine hair and urticaria. Three cases of mottling hypo-pigmentation (8.57%) and two cases of recurrence of melasma (5.71%) were recorded. CONCLUSION: Combination therapy with the MedLite C6 and 7% alpha arbutin solution is an effective and well-tolerated treatment for refractory melasma.