The elevated melanin production within the skin results in a distressing pigmentation disorder called melanoma. This underscores the importance of developing effective therapeutic approaches, such as nano-delivery systems. The primary objective of this research was to create alginate (AL) nanoparticle (NP) in gel dosage for improving targeting of arbutin (ARB) as a lightening substance to cure and manage melanoma cancer. Ionic gelation and ultrasonication method were employed to prepare ARB-AL-NP followed by In-vitro assessment of the NP. Outcomes noticed that the optimum ARB-AL-NP were in the size of 252.333 ± 11.873 nm with zeta potential -14.766 ± 0.862, greater encapsulation 89.831 ± 1.081%, and exhibited sustained release of ARB over 6 h (56%). In vitro MTT analysis confirmed that the optimum formulation had higher cell survival on the HFF cell line than kojic-acid and ARB, however, it showed a greater cytotoxic effect on the B16f10 cell line than other groups. Besides, ARB-AL-NP was established to obstruct melanogenesis to a superior level than kojic-acid and ARB and considerably suppress L-dopa auto-oxidation contrasted to kojic-acid and ARB). The outcomes of this assessment confirmed that the ARB-AL-NP could potentially serve as a prospective nanocarrier for ARB cutaneous application, thus unveiling novel approaches for addressing melanoma complaints.

IntroductionMethotrexate (MTX) is a widely utilized agent in the treatment of cancer, yet it is notable that it can induce pulmonary toxicity in cases of high-dose chemotherapy. Arbutin (ARB) is a hydroquinone compound that is present in members of the Lamiaceae, Ericaceae and Rosaceae families, and experimental studies have demonstrated its capacity for lung protection. The present study aimed to determine whether ARB could reduce the pulmonary toxicity of MTX and to explore the underlying mechanisms.MethodsThe lung toxicity rat model was created by means of a single intraperitoneal injection of MTX at a dose of 20 mg/kg. The animals were then treated with two different doses of ARB (50 and 100 mg/kg) for a period of 7 days. Following the conclusion of the treatment period, a histopathological examination of the lung tissue samples was conducted. The remaining tissue samples were evaluated for oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS), sirtuin 1 (SIRT1)/nuclear factor erythroid-related factor 2 (Nrf2) pathway, and apoptosis for further analysis.ResultsThe administration of MTX resulted in the inhibition of SIRT1/Nrf2 in lung tissue, accompanied by an escalation in OS, inflammation, ERS, and apoptosis levels. This was concomitant with a significant enhancement in the severity of histopathological findings. Nevertheless, ARB reversed MTX-induced biochemical and pathological changes through SIRT1/Nrf2 modulation.DiscussionIt is asserted that further comprehensive studies are required to support the hypothesis that ARB has the potential to improve oxidative and inflammatory lung injury via SIRT1/Nrf2 modulation.

Arbutin ameliorated depression by inhibiting neuroinflammation and modulating intestinal flora.

Modulation of Nrf-2/HO-1/HIF-1α/TFAM pathways by Arbutin in rat model of cerebral ischemic stroke.

Toxicological profiling and diuretic potential of arbutin via aldosterone synthase gene inhibition.

Arbutin improves lung injury in chicks induced by Mycoplasma gallisepticum infection

Understanding the interaction of therapeutic drugs with DNA is crucial for designing highly selective DNA-targeted medicines that could overcome the current therapeutic limitations. In this endeavour, the DNA binding behaviour of arbutin (ATN) was explored using multi-spectroscopic, electrochemical and computational studies. The UV-Vis spectral studies authenticated the complexation of ATN with CT-DNA and exposed ATN as a moderately strong DNA binder with a binding constant of 8.029 × 103 M−1. The findings of fluorescence spectral studies not only revealed the spontaneous ground state complex formation between ATN and CT-DNA, but also emphasised the role of hydrogen bonding and Van der Waals interactions in stabilising the ATN/CT-DNA complex. Since the competitive dye displacement assay strongly excluded the plausibility of classical intercalation and conventional groove binding mode of ATN, viscosity studies provided clues regarding the external binding mode of ATN. The appreciable enhancement resulted in the fluorescence emission of the ATN/CT-DNA complex upon increasing NaCl concentration, which certified ATN as an external binder. The CD spectral results exposed the ATN-induced moderate conformational alterations in CT-DNA. Remarkably, the voltammetric titration results labelled the glucopyranoside moiety of ATN as a DNA binding unit with a formation constant of 2.57 × 104 M−1 rather than the hydroquinone moiety of ATN. Molecular docking and metadynamics simulation outcomes served as pictorial evidence of experimental results. They revealed the predominant contribution of hydrogen bonding interactions in stabilising ATN/DNA complexation.

Development and efficacy of arbutin-loaded agarose hydrogel for antioxidant and depigmentation applications.

Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) are gaining attentions rapidly for inherent therapeutic values in skin care and cosmetics. However, the optimal combinations of ASC-sEVs and certain natural compounds for synergistic anti-aging effects have not been systematically studied. Human ASC-sEVs were purified from culture supernatant of ASCs and multi-omics datasets of miRNAs, proteins and lipids of ASC-sEVs were analyzed for pathways regulating skin homeostasis. ASC-sEVs were then loaded with nicotinamide riboside (NR), resveratrol (RES), vitamin C (VITC), retinol (RET) and arbutin (ARB) at different concentrations by the sonication-incubation method. Their anti-oxidant, anti-wrinkle and anti-melanogenic effects were tested invitro using the human keratinocyte HaCaT cells exposed to UVB radiation and human melanocyte B16F10 cells. Multi-omics data analysis of ASC-sEVs identified key bioactive molecules regulating collagen formation, pigmentation, oxidative stress and inflammation. In the invitro screenings for anti-aging effects, the compound-loaded ASC-sEVs outperformed the sEV- and compound-only treatments. Specifically in UVB-exposed HaCaT cells, 2 μg/mL sEVs loaded with 20 μg/mL NR, 2 μg/mL RES, 5 μg/mL VITC reduced reactive oxygen species level by 22.0%; while combination of sEVs and 2 μg/mL RES, 2.8 μg/mL RET significantly reduced MMP3 and upregulated PLOD1 expressions. B16F10 cells incubated with 2 μg/mL sEVs loaded with 2 μg/mL RES, 0.5 mM ARB had intracellular and extracellular melanin content lowered by 21.4% and 22.4% respectively. All the combinations caused no cytotoxicity. Our study demonstrated the superiority of ASC-sEVs to deliver both endogenous biocargos and exogenous compounds to achieve synergistic skin anti-aging effects.

Background: Arbutin (ARB) and quercetin (QUER) are two important phytoconstituents with proven anti-cancer effects. In vitro cytotoxic actions against a variety of tumor cell lines or antitumor-promoting properties have also been associated with extracts from Origanum majorana. Aim: To develop an easy, rapid, accurate, precise and reliable novel analytical method for the simultaneous estimation of quercetin and arbutin from Origanum majorana extracts and its marketed formulation. Method: The ideal chromatographic conditions for estimating arbutin and quercetin simultaneously using the RP-HPLC method are a stationary phase LichroCART C18 column (250mm × 4.0mm, 5μm), a mobile phase that contains 1% orthophosphoric acid and methanol in a 50:50% v/v ratio, a flow rate of 1 ml/min, ambient temperature operation, and a detection wavelength of 287 nm. The presence of arbutin and quercetin were qualitatively analyzed using mass spectroscopy. Results: The new RP-HPLC technique yielded a correlation value of 0.9999 and was demonstrated to be linear in the 0.5-2.5μg/ml range. Arbutin and quercetin were shown to have retention periods of 2.24 and 13.5 minutes, respectively. The amount of arbutin and quercetin in formulation were found to be 0.6484 μg and 0.1420 μg, respectively. The technique was validated using criteria such as specificity, accuracy, LOD, LOQ, precision, repeatability, stability, and system adaptability. Arbutin and quercetin were also confirmed to be present in the extract and formulation using mass spectroscopy (273 and 303 m/z values). Conclusion: Simple, fast, accurate, reliable, and economical, the suggested RP-HPLC and mass spectroscopy techniques are useful for consistently identifying arbutin and quercetin in both their prescription dose form and bulk. Major Findings: For arbutin and quercetin, the linearity was found to be between 0.5 and 2.5μg/ml, respectively. Among the extracts chloroform extract was found with separation of many components. The amount of arbutin and quercetin was determined to be 0.6484 μg and 0.1420 μg in the formulation.

Ethanobotanically, Operculina turpethum (O.T.) exhibits various therapeutic activities, including anti-inflammatory, hepatoprotective, anticancer, antiulcer, antidiabetic, and anthelmintic activity. However, the anthelmintic property lacks systematic investigation and exploration of mechanisms and responsible phytoconstituents. To elucidate the mechanistic basis of the anthelmintic activity of Operculina turpethum through in silico approaches, including ADMET profiling, molecular dynamics simulations, and KEGG pathway analysis. Additionally, to comprehensively evaluate the anthelmintic efficacy of its enriched extracts against Eisenia foetida through in vitro assays. Microwave-assisted extraction of Operculina turpethum with various solvents (petroleum ether, ethyl acetate, methanol, hydroalcoholic, and aqueous) was carried out to obtain numerous extracts. Evaluation of anthelmintic activity against Eisenia foetida earthworm using Piperazine citrate (PC) as a benchmark. Characterization of the most active extract (petroleum ether) using LC-MS. Furthermore, In silico analysis, ADMET, molecular docking, KEGG, and GO analysis of phytoconstituent with the target protein was carried out. Petroleum ether extract (PE) showed the most promising anthelmintic activity compared to other extracts and in comparison to the standard drug PC. LC-MS identified viniferifuran (VIN) and arbutin (ARB) in the PE extract. VIN exhibited the highest binding affinity (- 6.1kcal/mol) compared to the standard PC (- 2.4kcal/mol) and GABA ligand (- 2.9kcal/mol) in docking studies. In silico ADMET analysis predicted VIN to be non-carcinogenic and non-mutagenic. KEGG analysis revealed Viniferifuran's involvement in cAMP, cholinergic, and calcium signaling pathways, indicating its multi-target potential in mediating anthelmintic effects. PE extract displayed significant anthelmintic activity, potentially due to VIN, which acts through a GABA-mimetic mechanism. Operculina turpethum (O.T.) holds promise as a potential source for anthelmintic drug development.

Arbutin alleviates Mycoplasma gallinarum-induced damage caused by pulmonary fibrosis via the JAK2/STAT3 pathway

Background/Objectives: Dyslipidemia is frequently linked to various disorders, and its clinical relevance is now recognized. The role of inflammation and oxidative stress (OS) in dyslipidemia has been acknowledged. This study assessed the potential of arbutin (ARB) to prevent dyslipidemia and its associated OS and inflammation in rats with acute hyperlipidemia. Methods: Rats received ARB orally for 14 days and a single intraperitoneal injection of poloxamer-407 on day 15. Results: Poloxamer-407 elevated circulating cholesterol (CHOL), triglycerides (TG), very low-density lipoprotein (vLDL), and LDL, and reduced high-density lipoprotein (HDL)-C and lipoprotein lipase (LPL). ARB ameliorated the circulating lipids and LPL, and suppressed 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in rat liver and in vitro. Fatty acid synthase (FAS) in rat liver and its in vitro activity were suppressed by ARB, which also upregulated the LDL receptor (LDL-R) and ABCA1, and had no effect on ABCG5 and ABCG8 mRNA. ARB ameliorated liver malondialdehyde and nitric oxide and enhanced antioxidants in rats with dyslipidemia. Liver NF-κB p65 and blood inflammatory cytokines were increased in dyslipidemic rats, effects that were reversed by ARB. Moreover, ARB effectively suppressed lymphocyte E-NTPDase and E-ADA activities in dyslipidemic rats. The biochemical findings were supported by in silico data showing the affinity of ARB to bind LDL-R PCSK9 binding domain, HMGCR, FAS, and E-NTPDase. Conclusions: ARB possessed anti-dyslipidemia, anti-inflammatory, and antioxidant effects mediated via the modulation of CHOL and TG synthesis, LPL, lymphocyte E-NTPDase and E-ADA, and cytokine release in rats. Thus, ARB could be an effective agent to attenuate dyslipidemia and its associated OS and inflammation, pending further studies as well as clinical trials.

Heterocyclic phytometabolites formononetin and arbutin prevent in vitro oxidative and alkylation-induced mutagenicity

Temporary alleviation of MAPK by arbutin alleviates oxidative damage in the retina and ARPE-19 cells

Quantification of Arbutin and its degradation products, hydroquinone and p-Benzoquinone, in hyperpigmentation topical formulation: Effect of extraction procedure and interference assessment

Cisplatin is a potent anticancer agent widely employed in chemotherapy. However, cisplatin leads to toxicity on non-targeted healthy organs, including the liver. We investigated the hepatoprotective mechanism of arbutin (ARB), a glycosylated hydroquinone, against cisplatin-induced hepatotoxicity. Rats were orally administered with ARB (ARB1=50mg/kg; ARB2=100mg/kg) for 14 consecutive days against hepatotoxicity induced by a single dose of cisplatin (10mg/kg) on day 15. Three days after the intraperitoneal cisplatin injection, serum and liver tissue were collected for subsequent analyses. Cisplatin triggered marked increases in serum AST, ALT, and ALP activities, hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) coupled with a considerable diminution in hepatic activities of superoxide dismutase (SOD), catalase (CAT) and the concentration of reduced glutathione (GSH). The gene expressions of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and IL-6 were notably increased. The pre-administration of ARB1 and ARB2 reduced AST, ALT and ALP in serum and restored SOD, CAT, GSH, ROS, MDA and cytokine levels which was also evidenced by alleviated hepatic lesions. Further, cisplatin-induced prominent alterations in the gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), iNOS, NF-κB, Bax, Bcl-2, caspase-3 and 8-OHdG in the liver. Interestingly, ARB protected the liver and mitigated the cisplatin-induced alterations in serum AST, ALT, ALP, and reduced hepatic redox markers, 8-OdG, inflammatory markers and gene expressions. The findings demonstrate that ARB is a potential protective adjuvant against cisplatin-induced hepatotoxicity via inhibition of hepatic oxidative stress, inflammation, and apoptosis.

Realization of customizable performance castor oil-based waterborne polyurethane antiseptic coatings via arbutin

Novel multifunctional highly crosslinked bio-based waterborne polyurethane networks modified via long fatty hydrophobic side chains

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