[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.

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.

Anti-Toxoplasma In Vitro and In Vivo Activity of Pyrus boissieriana Arbutin-Rich Fraction.

PURPOSE: Pyrus boissieriana is a rich source of arbutin and has been used in herbal medicine to treat infectious diseases. This study aimed to investigate the effect of the arbutin-rich fraction of Pyrus boissieriana aerial parts on Toxoplasma gondii In Vitro and In Vivo. METHODS: An arbutin-rich fraction of P. boissieriana was prepared beforehand. Flow cytometry was used to evaluate the effect of different concentrations (1-512 µg/ml) of the P. boissieriana arbutin-rich fraction on Toxoplasma tachyzoites (RH strain). The cytotoxicity of the concentrations on the macrophage J774 cell line was also investigated by MTT assay. For In Vivo investigation, 4-6-week-old female mice infected with the RH strain of T. gondii were treated with different doses (16, 32, 64, 256, and 512 mg/kg) of the fraction using gavage. RESULTS: The highest and lowest lethality of the tachyzoites were 89.6% and 25.9% related to the concentrations of 512 µg/ml and 1 µg/ml, respectively, with an IC50 value of 18.1 µg/ml ± 0.37. The cytotoxicity test showed an IC50 value of 984.3 µg/ml ± 0.76 after 48 h incubation. The mean survival of mice at the lowest treated dose (16 mg/kg) was 6.6 days, and it was 15 days at the highest dose (512 mg/kg). The concentrations of 512, 256, 128, and 64 mg/kg of the fraction compared to the negative control (6.2 days mean survival) significantly increased the survival time of mice (P < 0.001, P = 0.009, P = 0.018, and P = 0.021, respectively). CONCLUSION: The results showed that the arbutin-rich fraction of P. boissieriana is effective against T. gondii In Vitro and In Vivo and may be a reliable alternative to conventional treatment for toxoplasmosis, although further studies are necessary.

Synergistic impact of arbutin and kaempferol-7-O-α-L-rhamnopyranoside from Nephelium lappaceum L. on whitening efficacy and stability of cosmetic formulations.

Four flavonoid glycosides, namely quercetin-3-O-rhamnoside (1), kaempferol-3-O-ß-D-glucopyranosyl (2), kaempferol-7-O-α-L-rhamnopyranoside (3), and kaempferol-3-O-ß-D-glucopyranosyl-7-O-α-L-rhamnopyranoside (4), from Nephelium lappaceum L. seeds were evaluated for their efficacy against melanin inhibition in B16F10 melanoma cells and tyrosinase inhibition. Among them, kaempferol-7-O-α-L-rhamnopyranoside (3) displayed the highest potency in both activities without any significant cytotoxicity. The combination of compound 3 and arbutin in specific proportions demonstrated a synergistic effect (CI < 1) in inhibiting melanin production in B16F10 cells and tyrosinase inhibition. Additionally, a cosmetic formulation containing compound 3 and arbutin as active ingredients exhibited favorable stability under accelerated storage conditions. Quantitative analysis indicated that compound 3 and arbutin levels in the formulation were above 90% after one month of storage. Determination of the formulation's shelf life using the Q10 method, estimating it to be around 5.2 months from the date of manufacture. The synergy between arbutin and kaempferol-7-O-α-L-rhamnopyranoside (3) extracted from N. lappaceum substantially enhances both the whitening effectiveness and the stability of cosmetic formulations.

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 inhibits androgen biosynthesis by rat immature Leydig cells in vitro.

Arbutin, a widely used skin lightening agent, has raised concerns regarding its potential side effects. In this study, we investigated the impact of arbutin on Leydig cell function using an in vitro model. We measured medium androgen levels, as well as the gene and protein expression related to Leydig cell steroidogenesis. Rat immature Leydig cells from age of 35 days were exposed to arbutin at concentrations ranging from 0.5 to 50 µM for a duration of 3 hrs. Following treatment, we observed a significant inhibition of androgen secretion by Leydig cells at both the 5 and 50 µM concentrations of arbutin. Furthermore, at a concentration of 50 µM, arbutin effectively blocked the stimulatory effects of luteinizing hormone (LH) and 8Br-cAMP on androgen secretion. Subsequent analysis revealed that arbutin downregulated the expression of crucial genes involved in androgen production, including Lhcgr, Hsd3b1, Cyp17a1, and Srd5a1. In silico computer program analysis predicted that arbutin exhibits good absorption, possesses a long elimination half-life, and may have other potential toxicity such as hepatoxicity. Taken together, our results demonstrate that arbutin negatively influences Leydig cell function and androgen production, potentially impacting male reproductive health.

Fabrication of polyvinyl pyrrolidone-K90/Eudragit RL100-based dissolving microneedle patches loaded with alpha-arbutin and resveratrol for skin depigmentation.

Alpha-arbutin (AA) and resveratrol (Res) are widely used in skin-lightening products. However, current topical formulations have minimal skin-lightening effects due to the low absorption and poor solubility of these active compounds. This study investigated the efficacy and safety of using dissolving microneedle (DMN) patches to improve the delivery of AA and Res for skin depigmentation. The DMN patches (F0-F3) fabricated from polyvinyl pyrrolidone-K90 (PVP-K90)/Eudragit RL100 blends successfully penetrated excised porcine skin and showed sufficient mechanical strength to resist compression forces. Loading DMNs with 10% AA and 2% Res at a ratio of 5 : 1 (F3) resulted in a synergistic interaction between the drugs with desirable dissolving ability, drug loading, and stability. Furthermore, both in vitro and in vivo studies revealed that the use of F3 DMN patches successfully enhanced the intradermal delivery of AA and Res over a 24 h period, with the delivered amount being higher (∼2.6 times) than that provided by a cream formulation (P < 0.05). After removing the DMN patches, the mice's skin was spontaneously and completely resealed within 12 h. In clinical studies, F3 DMN patches slightly decreased the melanin index of the participants without causing skin irritation or erythema at any time during the 24 h period when the patches were applied (P < 0.05). Moreover, application of the patches for 24 h was not found to affect skin hydration, transepidermal water loss, or skin elasticity. Therefore, AA/Res-loaded DMN patches could offer a promising approach for the effective local delivery of cosmetic agents for skin depigmentation.

Inhibitory Activities of Samples on Tyrosinases Were Affected by Enzyme Species and Sample Addition Methods.

The inhibition of tyrosinase (TYR) activity is an effective measure to inhibit melanin synthesis. At present, there are many methods with discrepant details that study the TYR inhibitory activity of samples. Under the same experimental conditions, this paper systematically studies whether enzyme species and sample addition methods are the key factors that determine the TYR inhibitory activity of samples. TYRs extracted from B16F10 cells, apple and mushroom, called BTYR, ATYR and MTYR, respectively, were selected to implement this study. Results showed that TYR inhibitory activities of samples were obviously affected by the above two factors. It was necessary to select the appropriate enzyme according to the problems to be explained. It was speculated that indirectly inhibitory activity reflected the comprehensive effects of samples on TYR catalytic activity and intracellular TYR synthesis pathway, while directly inhibitory activity reflected the effects of samples on TYR catalytic activity. Additionally, kojic acid could be used as a positive control for both B16F10 cells and MTYR models. The TYR inhibitory activity of ß-arbutin was complicated and fickle, while that of epigallocatechin gallate (EGCG) was universal and stable, which is to say, EGCG always inhibited TYR activity in a dose-dependent manner. In conclusion, the TYR inhibitory activities of samples were affected by enzyme species and sample addition methods. Compared with the unstable ß-arbutin, EGCG was more valuable for clinical research.

Arbutin abrogates testicular ischemia/reperfusion injury in rats through repression of inflammation and ER stress.

The aim of this study was to investigate the effects of arbutin (ARB) administration on oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis in an experimental testicular torsion/detorsion (T/D)-induced testicular injury model for the first time. A total of 24 male Sprague-Dawley rats were divided into four groups with six rats in each group: sham control, T/D, T/D+ARB (50 mg/kg) and T/D+ARB (100 mg/kg). Torsion and detorsion times were applied as 4 h and 2 h, respectively. The levels of lipid peroxidation [malondialdehyde (MDA)] and oxidative stress [total oxidant status (TOS) and total antioxidant status (TAS)] in testicular tissues were determined using colorimetric methods. The levels of DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)], antioxidant system [superoxide dismutase (SOD) and catalase (CAT)], pro-inflammatory cytokines [high mobility group box 1 (HMGB1), nuclear factor kappa B protein 65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and myeloperoxidase (MPO)], ER stress [78-kDa glucose-regulated protein (GRP78), activating transcription factor 6 (ATF6) and CCAAT-enhancer-binding protein homologous protein (CHOP)] and apoptosis (caspase-3) markers in testicular tissues were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. In the T/D group, it was determined that statistically significant increasing in the levels of oxidative stress, inflammation, ER stress and apoptosis compared with sham control group (p < 0.05). ARB administrations statistically significantly restored testicular I/R damage in a dose dependent manner (p < 0.05). In addition, it was determined that the data of histological examinations supported the biochemical results. Our findings support the hypothesis that ARB may be used as a protective agent against T/D-induced testicular damage.

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.

Efficient removal of Phaeocystis globosa from seawater with the persulfate activation by arbutin-modified cellulose nanocrystals.

Harmful algal blooms (HABs) from seawater have a severe threat to human health, aquaculture, and coastal nuclear power safety. Thus, it is highly desirable to explore environmentally friendly, efficient, and economic methods for controlling HABs. Herein, the arbutin-modified cellulose nanocrystals (AT-CNC) activated persulfate (PS), as a novel heterogeneous Fenton-like process, was proposed to remove Phaeocystis globosa (P. globosa) from seawater. The AT-CNC was synthesized via the surface modification of AT on CNC. The effects of AT dosage, CNC dosage, and PS dosage on the removal performance of P. globosa were investigated. With the addition of 530 mg/L AT-CNC (6 wt% AT/CNC of AT loading) and 120 mg/L PS, the removal percentage of chlorophyll a (Rc), optical density at 680 nm (Ro) and turbidity (Rt) reached 97.7%, 91.9% and 85.2% at 24 h. According to electron paramagnetic resonance (EPR) spectra and radical quenching tests, the predominant free radicals inactivating P. globosa were hydroxyl radicals (•OH). Additionally, the flocculation of the inactivated algae cells by AT-CNC was also critical for removing P. globosa. Moreover, a positive environmental impact was achieved in the AT-CNC-PS system due to the reduction of nitrogen, phosphorus and organic carbon contents. Based on the excellent removal performance for P. globosa, we believe that the AT-CNC activated persulfate is a promising option for HABs control.

The protective effect of arbutin against potassium bromate-induced oxidative damage in the rat brain.

This study aimed to investigate the protective effects of arbutin (ARB) against brain injury induced in rats with potassium bromate (KBrO3 ). The rats were divided into four groups as Group 1: Control (0.9% NaCl ml/kg/day p.), Group 2: KBrO3 (100 mg/kg (gavage), Group 3: ARB (50 mg/kg/day p.), and Group 4: KBrO3 + ARB (100 mg/kg (gavage) + 50 mg/kg/day p.). At the end of the fifth day of the study, the rats in all groups were killed, and their brain tissues were collected. In the collected brain tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were measured, and routine histopathological examinations were made. The MDA levels in the group that was exposed to KBrO3 were significantly higher than those in the control group (p ˂ 0.001). In comparison to the KBrO3 group, the MDA levels in the KBrO3 + ARB group were significantly lower (p ˂ 0.001). It was observed that SOD and CAT enzyme activity levels were significantly lower in the KBrO3 group compared to the control group (p ˂ 0.001), while these levels were significantly higher in the KBrO3 + ARB group than in the KBrO3 group (p ˂ 0.001). Additionally, the group that was subjected to KBrO3 toxicity, as well as ARB administration, had much lower levels of histopathologic signs than the group that was subjected to KBrO3 toxicity only. Consequently, it was found that KBrO3 exposure led to injury in the brain tissues of the rats, and using ARB was effective in preventing this injury.

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.

Anti-Toxoplasma gondii agent isolated from Orostachys malacophylla (Pallas) Fischer.

Botanical medicinal plants have aroused our interest to deal with Toxoplasmosis which can causes serious public health problems. Nipagic acid, gallic acid, ethyl gallate, phloretic acid, protocatechuic acid, methyl p-coumarate, arbutin, and homoprotocatechuic acid are first isolated from Orostachys malacophylla (Pallas) Fischer, their inhibition rate, survival rate, biochemical and viscera index are evaluated using gastric epithelia strain-1(GES-1). Among them, arbutin can effectively prolong the survival time of mice acutely infected with T. gondii, and exhibit the same curative effect as Spiramycin (Spi) group in terms of the glutathione (GSH) and malondialdehyde (MDA) content, alleviate hepatomegaly and splenomegaly. Structure-activity relationship (SAR) and molecular docking implies that phenolic hydroxyl group would be preferred for improvement of activity. In a summary, arbutin is a potential anti-T. gondii candidate for clinical application.

The melanin inhibitory effect of plants and phytochemicals: A systematic review.

BACKGROUND: Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of commercial whitening agents in managing skin melanin such as kojic acid and arbutin can lead to some negative effects such as dermatitis and liver cancer. Although past studies have researched the melanin inhibitory effect of plant extracts, the effective dose and mechanisms are not well summarized and discussed. This study aims to explore the melanin inhibitory property of phytochemicals and tries to answer the following research questions: (1) Which plant extracts and phytochemicals could inhibit melanin biosynthesis in the skin? what is the mechanism of action? (2) Have human trials been conducted to confirm their melanin inhibitory effect? (3) If not, which phytochemicals are recommended for further human trials? This article would provide information for future research to develop natural and safe skin whitening products. METHODS: A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review method and OHAT risk-of-bias tool were applied to screen literature from 2000 to 2021 and 50 research articles met the selection criteria. RESULTS: Flavonoids, phenolic acids, stilbenes and terpenes are main classes of phytochemicals responsible for the melanin inhibitory effects. The in vitro/in vivo melanin inhibitory effects of these plant extracts/phytochemicals are achieved via three main mechanisms: (1) the ethyl acetate extract of Oryza sativa Indica cv., and phytochemicals such as galangin and origanoside could manage melanin biosynthesis through competitive inhibition, non-competitive inhibition or mixed-type inhibition of tyrosinase; (2) phytochemicals such as ginsenoside F1, ginsenoside Rb1 and 4­hydroxy-3-methoxycinnamaldehyde could inhibit melanogenesis through down-regulating microphthalmia-related transcription factor (MITF) gene expression via different signalling pathways; (3) the ethanolic extracts of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius have a good ultraviolet absorption ability and high sun protective factor (SPF) values, thereby inhibiting UV induced melanogenesis in the skin. CONCLUSION: Although many plant extracts and phytochemicals have been found to inhibit melanin production, most of the results were only proved in cellular and/or animal models. Only the ethyl acetate extract of Oryza sativa Indica cv. panicle, and ginsenoside F1 were proved effective in human trials. Animal studies proved the effectiveness of galangin, origanoside, ginsenoside Rb1 and 4­hydroxy-3-methoxycinnamaldehyde with effective dose below 3 mM, and therefore recommended for future human trial. In addition, cellular studies have demonstrated the effectiveness of oxyresveratrol, mulberroside A, kurarinol, kuraridinol, plumbagin, (6aR,11aR)-3,8-dihydroxy-9­methoxy pterocarpan, ginsenoside Rh4, cardamonin, nobiletin, curcumin, ß-mangostin and emodin in inhibiting melanin synthesis at low concentrations of 20 µM and proved the low SPF values of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius extracts, and therefore recommended for further animal and human trials.

Timeline of the Development of Skin-Lightening Active Ingredients in Japan.

Japanese pharmaceutical cosmetics, often referred to as quasi-drugs, contain skin-lightening active ingredients formulated to prevent sun-induced pigment spots and freckles. Their mechanisms of action include suppressing melanin production in melanocytes and promoting epidermal growth to eliminate melanin more rapidly. For example, arbutin and rucinol are representative skin-lightening active ingredients that inhibit melanin production, and disodium adenosine monophosphate and dexpanthenol are skin-lightening active ingredients that inhibit melanin accumulation in the epidermis. In contrast, oral administration of vitamin C and tranexamic acid in pharmaceutical products can lighten freckles and melasma, and these products are more effective than quasi-drugs. On the basis of their clinical effectiveness, skin-lightening active ingredients can be divided into four categories according to their effectiveness and adverse effects. This review discusses academic research and development regarding skin-lightening ingredients in Japan.

Verification of the Protective Effects of Poplar Phenolic Compounds Against Poplar Anthracnose.

Poplar anthracnose caused by Colletotrichum gloeosporioides is one of the most important diseases widely distributed in poplar-growing areas in China, causing serious economic and ecological losses. In this study, three poplar species showed different resistance to poplar anthracnose: Populus × canadensis was resistant, Populus tomentosa was susceptible, and P. × beijingensis showed intermediate resistance. However, it remains uncertain whether phenolic compounds in poplar are involved in this resistance. Therefore, we determined the concentrations of phenolic compounds and their antifungal activity. Before and after the C. gloeosporioides inoculation, 20 phenolic compounds were detected in P. × canadensis and the number increased from 12 to 14 in P. × beijingensis but decreased from seven to four in P. tomentosa. Thus, phenolic compounds may be positively correlated with the degree of disease resistance. We selected seven phenolic compounds for further analysis, which varied considerably in content after inoculation with C. gloeosporioides. These seven compounds were salicin, arbutin, benzoic acid, salicylic acid, chlorogenic acid, ferulic acid, and naringenin, which helped poplar trees to limit the growth of C. gloeosporioides and differed in their antifungal effects, with phenolic acids having the strongest inhibitory effect. In addition, the optimal concentrations of different substances varied. We demonstrate that these phenolic compounds produced by poplar do play a certain role in the process of poplar resistance to anthracnose. These findings lay a foundation for future research into the antifungal mechanism of poplar trees and may be useful for enhancing the prevention and control of poplar anthracnose.

Effects of arbutin on glucose uptake by glucose transporter 4 (GLUT4) and its cytoprotective properties in L6 skeletal muscle cell line.

It has been well known that oxidative stress and increased intracellular reactive oxygen species (ROS) have a pivotal role in disrupting the insulin signaling pathways leading to cellular insulin resistance. In this study, we evaluated arbutin's effects on glucose uptake by GLUT4 and cytoprotective properties in the L6 skeletal muscle cell line. The effect of arbutin and tertiary butyl hydrogen peroxide (t-BHP) on glucose uptake in cultured L6 cells was investigated by flow cytometry. We also evaluated gene expression levels of GLUT1 and GLUT4 in the L6 cells by quantitative real-time polymerase chain reaction analysis. The results from the study demonstrated that the optimum ROS generation occurred 3 h after 100 µM t-BHP treatment and pretreatment with arbutin (500 and 1000 µM) significantly inhibited the t-BHP induced ROS generation (p < .05). Our result indicated that 3 h pretreatment of L6 cells with 1000 µM of arbutin before 50 µM t-BHP significantly increased glucose uptake than the 50 µM t-BHP alone group (p < .05). Our findings may suggest that an increase in the uptake of 2-NBDG by L6 cells with arbutin pretreatment can be associated with increased expression of GLUT4 and GLUT1 under oxidative stress.

Radioprotective Mechanisms of Arbutin: A Systematic Review.

PURPOSE: Efforts to produce radioprotective agents of high potential are appropriate strategies for overcoming possible IR toxicity in organisms. The present research aims to evaluate the signaling pathways and mechanisms through which arbutin exerts radioprotective effects on organisms. METHODS: The databases of PubMed, Web of Sciences, Google Scholar, and Scopus were searched to find studies that reported radioprotective effects for arbutin. Besides, the data were searched within the time period from 2010 to 2020. RESULTS: Five research articles met our criteria, which were included in the analysis based on their relevance to the topic. The present systematic review provides conclusions about various mechanisms and pathways through which arbutin induces radioprotection. CONCLUSIONS: Based on the relevant studies, various mechanisms can be proposed for inducing radioprotective effects by arbutin, including inhibition of oxidative stress, apoptosis, and inflammation.

Insertion Sequence (IS) Element-Mediated Activating Mutations of the Cryptic Aromatic ß-Glucoside Utilization (BglGFB) Operon Are Promoted by the Anti-Terminator Protein (BglG) in Escherichia coli.

The cryptic ß-glucoside GFB (bglGFB) operon in Escherichia coli (E. coli) can be activated by mutations arising under starvation conditions in the presence of an aromatic ß-glucoside. This may involve the insertion of an insertion sequence (IS) element into a "stress-induced DNA duplex destabilization" (SIDD) region upstream of the operon promoter, although other types of mutations can also activate the bgl operon. Here, we show that increased expression of the bglG gene, encoding a well-characterized transcriptional antiterminator, dramatically increases the frequency of both IS-mediated and IS-independent Bgl+ mutations occurring on salicin- and arbutin-containing agar plates. Both mutation rates increased with increasing levels of bglG expression but IS-mediated mutations were more prevalent at lower BglG levels. Mutations depended on the presence of both BglG and an aromatic ß-glucoside, and bglG expression did not influence IS insertion in other IS-activated operons tested. The N-terminal mRNA-binding domain of BglG was essential for mutational activation, and alteration of BglG's binding site in the mRNA nearly abolished Bgl+ mutant appearances. Increased bglG expression promoted residual bgl operon expression in parallel with the increases in mutation rates. Possible mechanisms are proposed explaining how BglG enhances the frequencies of bgl operon activating mutations.