The role of 755-nm alexandrite picosecond laser in melasma management.

Melasma is a skin dyspigmentation condition that disproportionately affects women, particularly those of Latino, Black, and Asian ethnicities, significantly impacting their quality of life. Efforts to identify effective treatment options have led to the exploration of picosecond laser technology which utilizes brief pulse durations to break down pigment while minimizing thermal damage to surrounding tissue. The 755-nm alexandrite picosecond laser, currently FDA approved for benign pigmented lesion removal, including melasma, is a promising solution. We aim to assess the efficacy and safety of the 755-nm alexandrite picosecond laser both as a stand-alone treatment for melasma and in combination with topical agents. We conducted a PubMed search using "755-nm picosecond" AND "melasma," "755-nm picosecond" AND "hydroquinone," and "755-nm picosecond" AND "tranexamic acid." English-written studies examining this laser as monotherapy or in combination with the topical agents were included. Those not meeting the criteria or lacking data related to melasma improvement were excluded. Monotherapy with the 755-nm picosecond laser led to a 50-75% improvement in melasma appearance in 40% of participants and a significant reduction in the average Melasma Area and Severity Index (MASI) score (p < 0.001) in all patients of one study. Notably, the use of topical tranexamic acid (TTA) in conjunction with the picosecond laser exhibited the most significant degree of improvement in hemi-MASI scores compared to the laser monotherapy group at one- and three-months post-treatment (p < 0.05). Patient satisfaction was also significantly higher for the combination group (p < 0.05). In contrast, combining hydroquinone (HQ) with the picosecond laser demonstrated no significant difference in outcomes compared to HQ alone, both of which were less effective than TTA with picosecond laser. The combination of the 755-nm picosecond laser with TTA proves promising, outperforming both laser monotherapy and laser with HQ. While monotherapy with the picosecond laser or topical agents is effective, literature favors combination therapy, especially the 755-nm picosecond laser with TTA, for superior benefits and minimal side effects. Ultimately, individualized regimens, considering factors like skin type, should be prioritized, given the heightened risk of postinflammatory hyperpigmentation, especially in skin of color patients.

Efficacy of photorejuvenation combined with tranexamic acid and hydroquinone cream in the treatment of complex facial pigmentation.

The aim of this study was to assess the effectiveness of photo rejuvenation combined with tranexamic acid and hydroquinone cream in the treatment of complex facial pigmentation. A total of 108 patients with complex facial pigmentation between October 2019 and October 2021 were included in this retrospective study and divided into 2 groups according to the treatment that they received, with 54 cases in each group. The control group received treatment with tranexamic acid and hydroquinone cream. On the basis of the control group, the observation group was treated with photo rejuvenation combined with tranexamic acid and hydroquinone cream. The effectiveness of the treatments in both groups was determined through photographs and melasma area severity index score. The skin conditions were also compared before and after treatment. The effective rate of the observation group was significantly higher than that of the control group (98.15% vs 83.33%, P = .025). The melasma area and severity index score in the observation group was significantly lower than that in the control group after treatment (1.58 ±â€…0.14 vs 2.96 ±â€…0.13, P < .001). Before treatment, there was no significant difference in the skin elasticity and skin water content between the observation group and control group (P > .05). After treatment, the skin elasticity and skin water content were significantly higher than that in the control group (P < .05). Photo rejuvenation combined with tranexamic acid and hydroquinone cream has a significant curative effect on patients with complex facial pigmentation, which can significantly improve skin elasticity, increase skin water content, and reduce the degree of skin lesions.

Regulation of mitochondrial function by hydroquinone derivatives as prevention of platelet activation.

Platelet activation plays an essential role in the pathogenesis of thrombotic events in different diseases (e.g., cancer, type 2 diabetes, Alzheimer's, and cardiovascular diseases, and even in patients diagnosed with coronavirus disease 2019). Therefore, antiplatelet therapy is essential to reduce thrombus formation. However, the utility of current antiplatelet drugs is limited. Therefore, identifying novel antiplatelet compounds is very important in developing new drugs. In this context, the involvement of mitochondrial function as an efficient energy source required for platelet activation is currently accepted; however, its contribution as an antiplatelet target still has little been exploited. Regarding this, the intramolecular hydrogen bonding of hydroquinone derivatives has been described as a structural motif that allows the reach of small molecules at mitochondria, which can exert antiplatelet activity, among others. In this review, we describe the role of mitochondrial function in platelet activation and how hydroquinone derivatives exert antiplatelet activity through mitochondrial regulation.

Neuroprotective Effects of Phenolic Antioxidant Tert-butylhydroquinone (tBHQ) in Brain Diseases.

Human life and health are gravely threatened by brain diseases. The onset and progression of the illnesses are influenced by a variety of factors, including pathogenic causes, environmental factors, mental issues, etc. According to scientific studies, neuroinflammation and oxidative stress play a significant role in the development and incidence of brain diseases by producing pro-inflammatory cytokines and oxidative tissue damage to induce inflammation and apoptosis. Neuroinflammation, oxidative stress, and oxidative stress-related changes are inseparable factors in the etiology of several brain diseases. Numerous neurodegenerative diseases have undergone substantial research into the therapeutic alternatives that target oxidative stress, the function of oxidative stress, and the possible therapeutic use of antioxidants. Formerly, tBHQ is a synthetic phenolic antioxidant, which has been widely used as a food additive. According to recent researches, tBHQ can suppress the processes that lead to neuroinflammation and oxidative stress, which offers a fresh approach to treating brain diseases. In order to achieve the goal of decreasing inflammation and apoptosis, tBHQ is a specialized nuclear factor erythroid 2-related factor (Nrf2) activator that decreases oxidative stress and enhances antioxidant status by upregulating the Nrf2 gene and reducing nuclear factor kappa-B (NF-κB) activity. This article reviews the effects of tBHQ on neuroinflammation and oxidative stress in recent years and looks into how tBHQ inhibits neuroinflammation and oxidative stress through human, animal, and cell experiments to play a neuroprotective role in Alzheimer's disease (AD), stroke, depression, and Parkinson's disease (PD). It is anticipated that this article will be useful as a reference for upcoming research and the creation of drugs to treat brain diseases.

Split-face comparison of hydroquinone 4% plus nitrogen plasma vs. hydroquinone 4% alone in the treatment of melasma.

Treatment of skin diseases is important yet challenging. One of the most common skin diseases in women is melasma, which features acquired facial hyperpigmentation. We studied the effect of cold atmospheric nitrogen plasma on this disease. To characterize the nitrogen plasma, we obtained the relative intensity of the species and the plasma temperature and skin temperature during processing at different input powers and gas flows. Patients complaining of melasma were treated with hydroquinone on both sides of the face, and one side was randomly selected for additional nitrogen plasma therapy. Eight treatment sessions of plasma processing were provided 1 week apart, and one follow-up session was scheduled 1 month after the end of treatment. The rate of improvement was scored by a dermatologist in the eighth session and 1 month following the last session using the modified Melasma Area Severity Index (mMASI). Skin biomechanical characteristics such as melanin, cutaneous resonance running time (CRRT), transepidermal water loss (TEWL), and hydration were measured at baseline and during the fourth, eighth, and follow-up sessions. On both sides, we observed a significant decrease in both CRRT and melanin (P < 0.05). TEWL did not change on both sides, while hydration decreased significantly only on the side to which hydroquinone was applied in isolation (P < 0.05). According to clinical scores, on both sides, we had significant improvement. On the side that plasma was not applied, the percentage reduction of pigmentation (mMASI) in the eighth and follow-up sessions in comparison with the baseline was 5.49 ± 8.50% and 33.04 ± 9.17%, respectively, while on the other side, these figures were 20.57 ± 6.64% and 48.11 ± 11%. For melanin, these figures were 13.84 ± 4.84% and 18.23 ± 7.10% on the hydroquinone side and 21.56 ± 3.13% and 23.93 ± 3.02% on the other side. According to these results, nitrogen plasma can safely complement topical hydroquinone to improve clinical outcomes when treating melasma without causing stratum corneum damage or skin discomfort, though confirmatory studies are needed.

Hydroquinone cream-based polymer microneedle roller for the combined treatment of large-area chloasma.

Melasma is a common hyperpigmented skin condition that occurs on the face and other areas prone to light exposure, seriously affecting people's quality of life. Microneedle, a new type of transdermal drug delivery device, can significantly improve skin permeability. In this study, we designed and fabricated a polymer microneedle roller (PMR) using a mold hot pressing method, and established a mouse model of melasma induced by ultraviolet radiation. The dynamometer and insertion test of MNs into parafilm and skin of mice indicates that the MNs have sufficient mechanical properties to insert parafilm and skin of mice. The two methods (apply hydroquinone cream (HQC) directly and pre-treat with PMR before applying HQC) were used to treat melasma. From the results of skin surface observation, determination of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in skin and liver tissues, histological observation, and skin Optical coherence tomography (OCT), we confirmed both the two methods had a therapeutic effect while the PMR pretreatment group exhibited a better therapeutic effect. In addition, there were statistical differences between the UV group (P < 0.05). Together these results indicated that the MNs may be promising in future clinical applications in improving the UV irradiation-induced pigmentation like melisma.

Perspectives of topical formulations for melasma.

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.

Combination of a 755-nm picosecond laser and hydroquinone 2% cream versus hydroquinone 2% cream alone for the treatment of melasma: A randomized, split-face, and controlled trial.

BACKGROUND: While combined laser and topical treatments are currently a common approach to melasma treatment, data on the efficacy and safety of this combined therapy remain scarce, with studies showing varied results. OBJECTIVE: To compare the efficacy and safety of hydroquinone (HQ) cream alone versus HQ cream combined with 755-nm picosecond (PS) laser in the treatment of melasma. METHOD: Twenty subjects presenting with mixed-type melasma were enrolled in the study. All patients were instructed to apply 2% HQ cream to both sides of the face for 4 weeks. Randomly assigned hemifaces of all patients thereafter received 5 biweekly PS laser treatments. Objective (measurement of average melanin content and melanin index) and subjective (grading of modified melasma area and severity index [mMASI] score and global percentage of pigment clearance) assessments of melasma clearance, and occurrence of adverse effects were evaluated at 1-, 3-, and 6-months after the final laser treatment. RESULTS: mMASI scores were significantly improved from baseline for both sides (p = 0.006 HQ alone, p < 0.001 HQ + PS laser), with no statistically significant difference when comparing HQ alone versus HQ + PS laser. Objective assessments (measurements of average melanin content and melanin index) of melasma clearance corresponded to the clinical evaluation using mMASI score. Mild postinflammatory hyperpigmentation was observed in 15% of the patients on the laser-treated side, while no adverse effects were reported on the HQ monotherapy side. CONCLUSIONS: Adjunctive treatment with a 755-nm PS laser does not provide additional benefit to topical HQ in the treatment of melasma. ClinicalTrail.gov PRS. number: NCT04597203.

Characterization of the activity and the mechanism of action of a new toluquinol derivative with improved potential as an antiangiogenic drug.

The inhibition of sustained angiogenesis is an attractive approach for the treatment of cancer, blindness and other angiogenesis-dependent diseases. Encouraged by our previous finding that toluquinol, a methyl hydroquinone isolated from a marine fungus, exhibited an interesting antiangiogenic activity, we further explored structural modifications of this natural compound in order to develop improved drug candidates. Our results indicate that although the methyl group plays a relevant role in the cytotoxic activity of toluquinol, some derivatives in which this methyl was replaced by another substituent, could keep the antiangiogenic activity, whereas exhibiting a lower cytotoxicity in vitro. This is the case of (E)- 2-(3-methoxyprop-1-en-1-yl) benzene-1,4-diol, which exhibits a decreased toxicity, whereas maintaining or even improving the antiangiogenic activity of toluquinol, as demonstrated by a number of in vitro (endothelial cells proliferation, migration and tube formation) and in vivo (chick embryo chrorioallantoic membrane vascularization and murine corneal neovascularization) experimental approaches. Our results point to a mechanism of action that could be related to an induction of apoptosis, as well as to an increase in the reactive oxygen species levels, a reduction of the redox capacity and the inhibition of the VEGFR2, Akt and ERK phosphorylation in VEGF-activated endothelial cells. The biological activity of this new angiogenesis inhibitor, along with its lower undesired toxicity, suggests that it is a promising drug candidate with improved potential for the treatment of angiogenesis-related diseases.

Understanding Melasma-How Can Pharmacology and Cosmetology Procedures and Prevention Help to Achieve Optimal Treatment Results? A Narrative Review.

Melasma is a chronic skin condition that involves the overproduction of melanin in areas exposed to ultraviolet radiation. Melasma treatment is long-term and complicated with recurrence and resistance to treatment. The pathogenesis of melasma is highly complex with multiple pathologies occurring outside of the skin pigment cells. It includes photoaging, excessive melanogenesis, an increased number of mast cells, increased vascularization, and basement membrane damage. In addition, skin lesions related to melasma and their surrounding skin have nearly 300 genes differentially expressed from healthy skin. Traditionally, melasma was treated with topical agents, including hydroquinone, tretinoin, glucocorticosteroids and various formulations; however, the current approach includes the topical application of a variety of substances, chemical peels, laser and light treatments, mesotherapy, microneedling and/or the use of systemic therapy. The treatment plan for patients with melasma begins with the elimination of risk factors, strict protection against ultraviolet radiation, and the topical use of lightening agents. Hyperpigmentation treatment alone can be ineffective unless combined with regenerative methods and photoprotection. In this review, we show that in-depth knowledge associated with proper communication and the establishment of a relationship with the patient help to achieve good adherence and compliance in this long-term, time-consuming and difficult procedure.

Tert-butylhydroquinone protects the retina from oxidative stress in STZ-induced diabetic rats via the PI3K/Akt/eNOS pathway.

This study aims to investigate whether tert-butylhydroquinone protects the retina from oxidative stress in STZ-induced experimental diabetic rats through the activation of phosphinositide 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) pathway.In vitro, NO, reactive oxygen species(ROS), eNOS, p-eNOS Ser1179, Akt, p-Akt Ser473 and L-NAME protein expression was analyzed within rMC-1 cells cultivated within normal control(NC), high glucose (HG) and HG-containing tert-butyl hydroquinone (tBHQ) (5 µM) medium. We confirmed tBHQ's protection through administering inhibitors of PI3K and Akt. In vivo, tBHQ was administered at a ratio of 1% (w/w) to diabetic rats was induced through an STZ injection (65 mg/kg) for a 3-month period, and the retinal expression of eNOS, p-eNOS Ser1179, Akt, and p-Akt Ser473 proteins was measured using Western blotting (WB) assay. We also utilized the TUNEL kit for detecting retinal cell apoptosis. The changes of retinal morphology and visual function were measured by performing hematoxylin-eosin staining (HE staining) and electroretinograms. In vitro, ROS levels were increased in the high glucose group, NO levels were decreased, and the relative expression of Akt/p-Akt Ser473 and eNOs/p-eNOS Ser1179 was reduced. tBHQ abolished these changes, and these effects were suppressed by specific inhibitors. In vivo, tBHQ upregulated retinal protein expression in STZ-induced diabetic rats, reduced retinal apoptotic cell numbers, and partially prevented abnormalities in retinal function and structure caused by diabetes. tBHQ alleviates oxidative stress during diabetic retinopathy by upregulating the PI3K/Akt/eNOS pathway and partially restoring the structure and function of the retina. It may play a role in delaying vision loss caused by diabetic retinopathy.

Medical therapies for melasma.

Melasma is a common malady affecting all races with a higher incidence in Hispanics, Middle Eastern, Asians, and African origin females (Fitzpatrick skin phototypes III-V). Women are affected much more often than men. Melasma remains a significant cause of cosmetic morbidity and psychosocial embarrassment affecting quality of life necessitating effective and reliable treatment. Unfortunately, treatment remains unsatisfactory due to limited efficacy, adverse effects, and relapses after stopping treatment. Although chemical peels, laser and light therapies and dermabrasion may have utility, the evidence available for their efficacy is limited and they often cause post-inflammatory hyperpigmentation, particularly in individuals with darker skin types. Medical therapies remain mainstay in the management of melasma. The triple combination, hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% (Triluma, Galderma, Ft. Worth Texas, often modified incorporating different corticosteroids) remains the only US FDA-approved treatment for melasma and is the gold standard due its demonstrated efficacy across ethnicities. Oral tranexamic acid alone or in combination with other modalities has also shown significant efficacy. Several cosmeceuticals and botanical extracts used as skin lightening agents have been demonstrated to be useful. Physical sunscreens containing zinc oxide, iron oxide, titanium dioxide, and silicones provide photoprotective and camouflage effect. We propose that a multimodality approach to the treatment of melasma is the most effective treatment approach. This review is focused on the medical therapies for melasma.

Role of Platelet-Rich Plasma Therapy as an Adjuvant in Treatment of Melasma.

BACKGROUND: The management of melasma is an ongoing challenge. Platelet-rich plasma (PRP) therapy has been reported to be beneficial, but there is paucity of studies on PRP therapy in melasma. OBJECTIVE: To compare the efficacy of PRP therapy and hydroquinone versus hydroquinone alone in melasma. MATERIALS AND METHODS: Thirty patients were randomized to receive PRP microinjections on one side and normal saline on the other in a total of 3 sittings. Patients were concurrently advised 4% hydroquinone (HQ) cream application on both sides of the face. Efficacy was evaluated with hemi-modified Melasma Area Severity Index (MASI) scoring and a 4-scale patient satisfaction grading. RESULTS: Majority of the subjects (53.3%) in PRP + HQ group and 76.7% in HQ group had 25% to 50% improvement in their MASI scores. However, 40% in the PRP + HQ group and only 3.3% in the HQ group had 51% to 75% improvement. The difference in the percentage improvement was statistically significant. There was a greater percentage of subjects reporting a good response among the HQ + PRP group (53.3%) as compared with the HQ group (27%). CONCLUSION: Microinjections of PRP combined with topical HQ has better efficacy than topical HQ alone.

Liposomal azelaic acid 20% cream vs hydroquinone 4% cream as adjuvant to oral tranexamic acid in melasma: a comparative study.

BACKGROUND: Melasma negatively impacts patient's quality of life (QoL). Although hydroquinone 4% is the most prescribed treatment, several side effects had been reported. The traditionally used azelaic acid 20% has poor tolerability and low skin absorption rate. AIM: To assess the efficacy and tolerability of the liposomal form of azelaic acid 20% as an adjuvant to oral tranexamic acid in the treatment of melasma. PATIENTS AND METHODS: Fifty females suffering from melasma were divided into two equal groups. The first group used a liposomal form of azelaic acid 20%, and the second group used hydroquinone 4%. Oral tranexamic acid 250 mg was taken by both groups as a single oral daily dose. Melasma severity and the patient's QoL were assessed. RESULTS: A significant improvement of melasma was detected in females who used the liposomal form of azelaic acid 20% than those who used hydroquinone 4%. This was associated with a significant positive effect on their QoL. Furthermore, the liposomal form of azelaic acid 20% was more significantly tolerable than hydroquinone 4%. CONCLUSION: The use of the liposomal form of azelaic acid provides an effective and well-tolerated addition to the treatment of melasma.

Fractional erbium:YAG laser (2940 nm) plus topical hydroquinone compared to intradermal tranexamic acid plus topical hydroquinone for the treatment of refractory melasma: a randomized controlled trial.

OBJECTIVES: Melasma is a chronic acquired condition characterized by grayish-brown macules and patches with a distinct border on the face. Although various treatments methods have been suggested for treating melasma, none has been completely successful. The aim of the study was to compare the efficiency of erbium: yttrium-aluminum-garnet (Er:YAG) laser and 4% hydroquinone (HQ) with the effects of intradermal tranexamic acid (TA) and 4% HQ for the treatment of refractory melasma. METHODS: The study included 31 female patients with refractory melasma. The left or right side of the patient's face was chosen randomly to receive laser therapy with topical HQ on the one side (i.e. the laser side) and intradermal injection of TA plus topical HQ on the other side (i.e. the mesotherapy side). Digital photography was performed at baseline, at the end of the treatment, and three months after the treatment as follow-up. Two independent dermatologists evaluated the modified Melasma Area and Severity Index (mMASI) score according to the pictures. Overall, 27 patients completed the study and went through the clinical evaluation. RESULTS: Treatment using HQ in combination with either Er:YAG laser therapy or intradermal injection of TA significantly improved the hemi-mMASI and resulted in higher patient satisfaction. While the improvement was not significantly different between the two regiments after the treatment and upon follow up and both were equally efficient in the treatment of refractory melasma (p = 1.308), recurrence rate was higher after treatment with Er:YAG laser than TA (12% vs 34%). CONCLUSION: This study confirmed the comparable efficacy of TA plus topical HQ versus Er:YAG laser plus topical HQ for the treatment of refractory melasma. Both groups improved significantly and no subject left the treatment because of adverse effects. TRIAL REGISTRATION NUMBER: IRCT20191011045057N1.

Topical Cyperus rotundus essential oil for treatment of axillary hyperpigmentation: a randomized, double-blind, active- and placebo-controlled study.

BACKGROUND: The oil of the grass Cyperus rotundus (purple nutsedge) is an effective and safe treatment option for a variety of conditions. It has anti-inflammatory and antipigmenting properties. There have been no clinical trials comparing topical C. rotundus oil with skin-lightening treatments for axillary hyperpigmentation. AIM: To assess the efficacy of C. rotundus essential oil (CREO) in treating axillary hyperpigmentation, and compare with another active treatment hydroquinone (HQ) and a placebo (cold cream) in this study. METHODS: The study included 153 participants, who were assigned to one of three study groups: CREO, HQ group or placebo group. A tri-stimulus colorimeter was used to assess pigmentation and erythema. Two independent experts completed the Physician Global Assessment, and the patients completed a self-assessment questionnaire. RESULTS: CREO had significantly (P < 0.001) better depigmenting effects than HQ. CREO and HQ did not differ significantly in terms of depigmentation effects (P > 0.05); however, there were statistically significant differences in anti-inflammatory effects and decrease in hair growth (P < 0.05) in favour of CREO. CONCLUSIONS: CREO is a cost-effective and safe treatment for axillary hyperpigmentation.

BTT-105 ameliorates hepatic fibrosis in non-alcoholic fatty liver animal model.

BTT-105 (1-O-hexyl-2,3,5-trimethylhydroquinone), a hydroquinone derivative, is a potent anti-oxidant that was safe and tolerable in phase I clinical trial. This study examined the anti-fibrotic effect of BTT-105 in a mouse model of non-alcoholic fatty liver disease (NAFLD) along with the underlying mechanisms. In vivo, efficacy of BTT-105 evaluated from three kinds of NAFLD models (methionine/choline deficient diet (MCD), high fat diet (HF) and western diet (WD)). Metabolomics and transcriptomics profiling analysis in liver tissues were conducted. In vitro, anti-fibrotic effect of BTT-105 assessed in human hepatic stellated cells (HSCs) and primary mouse HSCs. BTT-105 improved NAFLD activity score in three kinds of NAFLD animal models (MCD, HF, and WD). BTT-105 also decreased levels of hepatic pro-collagen and collagen fibers deposition in liver tissue. Metabolome and transcriptome analysis revealed that BTT-105 decreased lipid metabolites and increased antioxidants in NAFLD mice. In HepG2 cells, BTT-105 enhanced Nrf2-ARE reporter activity in a dose-dependent manner and increased the levels of antioxidant gene expression. BTT-105 showed inhibition of HSCs activation and migration. Gene expression profiling and protein expression showed that BTT-105 increased Nrf2 activation as well as decreased PI3K-Akt pathway in activated HSCs. BTT-105 attenuated ameliorates steatohepatitis and hepatic fibrosis.