Transcriptomic screening of novel targets of sericin in human hepatocellular carcinoma cells.

Sericin, a natural protein derived from Bombyx mori, is known to ameliorate liver tissue damage; however, its molecular mechanism remains unclear. Herein, we aimed to identify the possible novel targets of sericin in hepatocytes and related cellular pathways. RNA sequencing analysis indicated that a low dose of sericin resulted in 18 differentially expressed genes (DEGs) being upregulated and 68 DEGs being downregulated, while 61 DEGs were upregulated and 265 DEGs were downregulated in response to a high dose of sericin (FDR ≤ 0.05, fold change > 1.50). Functional analysis revealed that a low dose of sericin regulated pathways associated with the complement and coagulation cascade, metallothionine, and histone demethylate (HDMs), whereas a high dose of sericin was associated with pathways involved in lipid metabolism, mitogen-activated protein kinase (MAPK) signaling and autophagy. The gene network analysis highlighted twelve genes, A2M, SERPINA5, MT2A, MT1G, MT1E, ARID5B, POU2F1, APOB, TRAF6, HSPA8, FGFR1, and OGT, as novel targets of sericin. Network analysis of transcription factor activity revealed that sericin affects NFE2L2, TFAP2C, STAT1, GATA3, CREB1 and CEBPA. Additionally, the protective effects of sericin depended on the counterregulation of APOB, POU2F1, OGT, TRAF6, and HSPA5. These findings suggest that sericin exerts hepatoprotective effects through diverse pathways at different doses, providing novel potential targets for the treatment of liver diseases.

Sericin enhances ammonia detoxification by promotes urea cycle enzyme genes and activates hepatic autophagy in relation to CARD-9/MAPK pathway.

Urea cycle is an important metabolic process that initiates in liver mitochondria and converts ammonia to urea. The impairment of ammonia detoxification, both primary and secondary causes, lead to hyperammonemia, a life-threatening condition affecting to the brain. Current treatments are not enough effective. In addition, our recent proteomics study in hypercholesterolemic rat model demonstrated that sericin enhances hepatic nitrogenous waste removal through carbamoyl-phosphate synthase 1 (CPS-1), aldehyde dehydrogenase-2 (ALDH-2), and uricase proteins. However, the underlining mechanisms regard to this property is not clarified yet. Therefore, the present study aims to examine the effect of sericin on urea cycle enzyme genes (CPS-1 and ornithine transcarbamylase; OTC) and proteins (mitogen-activated protein kinase; MAPK, caspase recruitment domain-containing protein 9; CARD-9, Microtubule-associated protein light chain 3; LC-3), which relate to urea production and liver homeostasis in hepatic cell line (HepG2) and hypercholesterolemic rat treated with or without sericin. qRT-PCR, immunohistochemistry, and electron microscopy techniques were performed. In vitro study determined that high dose of sericin at 1 mg/ml increased liver detoxification enzyme (Cytochrome P450 1A2; CYP1A2 and ALDH-2) and urea cycle enzyme (CPS-1 and OTC) genes. Both in HepG2 cell and rat liver mitochondria, sericin significantly downregulated CARD-9 (apoptotic protein) expression while upregulated MAPK (hepatic homeostasis protein) and LC-3 (autophagic protein) expressions. Hence, it might be concluded that sericin promotes ammonia detoxification by both increases urea cycle enzyme genes and enhances hepatic autophagy in associated with CARD-9/MAPK pathway (as shown by their own negative relationship). This study presents another beneficial property of sericin to develop an upcoming candidate for ammonia toxicity alleviation and liver function improvement.

Sericin-Based Poly(Vinyl) Alcohol Relieves Plaque and Epidermal Lesions in Psoriasis; a Chance for Dressing Development in a Specific Area.

The noncontagious immune-mediated skin disease known as psoriasis is regarded as a chronic skin condition with a 0.09-11.4% global prevalence. The main obstacle to the eradication of the disease continues to be insufficient treatment options. Sericin, a natural biopolymer from Bombyx mori cocoons, can improve skin conditions via its immunomodulatory effect. Many external therapeutic methods are currently used to treat psoriasis, but sericin-based hydrogel is not yet used to treat plaques of eczema. Through the use of an imiquimod rat model, this study sought to identify the physical and chemical characteristics of a silk sericin-based poly(vinyl) alcohol (SS/PVA) hydrogel and assess both its therapeutic and toxic effects on psoriasis. The cytokines, chemokines, and genes involved in the pathogenesis of psoriasis were investigated, focusing on the immuno-pathological relationships. We discovered that the SS/PVA had a stable fabrication and proper release. Additionally, the anti-inflammatory, antioxidant, and anti-apoptotic properties of SS/PVA reduced the severity of psoriasis in both gross and microscopic skin lesions. This was demonstrated by a decrease in the epidermal histopathology score, upregulation of nuclear factor erythroid 2-related factor 2 and interleukin (IL)-10, and a decrease in the expression of tumor necrosis factor (TNF)-α and IL-20. Moreover, the genes S100a7a and S100a14 were downregulated. Additionally, in rats given the SS/PVA treatment, blood urea nitrogen, creatinine, and serum glutamic oxaloacetic transaminase levels were within normal limits. Our findings indicate that SS/PVA is safe and may be potentiated to treat psoriasis in a variety of forms and locations of plaque because of its physical, chemical, and biological characteristics.

Expression Pattern of Genes in Condyloma Acuminata Treated with Clinacanthus nutans Lindau Cream versus Podophyllin.

Clinacanthus nutans Lindua (C. nutans), a strong antiviral traditional medicine, can be used to treat condyloma acuminata (CA) caused by the human papillomavirus (HPV). However, its molecular mechanism for CA elimination is unknown. Herein, we conducted a randomized clinical trial to evaluate the effectiveness of C. nutans and its molecular mechanism compared with podophyllin, the gold standard treatment. Using a randomized block design, six patients were treated with C. nutans and podophyllin for four weeks. Efficacy of drugs was assessed by size reduction of the warts and HPV viral load quantification using droplet digital PCR. The gene expression profiling of CA was analyzed using NanoString Technology. After the podophyllin and C. nutans treatments, CA lesion sizes were reduced to 97.0% and 84.4% clearance, and the HPV viral loads were reduced by 74.0% and 46.6%, respectively. The gene expression pattern of immune profiling showed that 23 genes (i.e., HLA-DPB, CCL3, CXCL2, CXCR2, and OSM) were significantly differentially expressed by podophyllin, whereas 2 genes (IFNL1 and IRF2) were remarkably expressed by C. nutans. In inflammatory profiling, 108 genes (i.e., CXCL2, IL8, and STAT3) were highly expressed by podophyllin, but none of genes were observed to change expression by C. nutans. These results suggested that podophyllin may reduce the HPV infection through a mechanism related to proinflammatory response. In addition, C. nutans was found to suppress the HPV infection through mechanism related to the activation of immune response. This study shows novel therapeutic mechanisms of podophyllin and C. nutans. It is suggested that C. nutans might be used as an alternative treatment for CA treatment.

A combination extract of kaffir lime, galangal, and lemongrass maintains blood lipid profiles, hepatocytes, and liver mitochondria in rats with nonalcoholic steatohepatitis.

Kaffir lime leaves and the rhizomes of galangal and lemongrass are the main ingredients in several Thai foods with desirable medicinal effects. Based on their beneficial activities, this study aimed to indicate the chemical properties and in vivo efficacy of a combination of the herbs at a 1:2:1 ratio in a water extract form. Its volatile constituents were analyzed by gas chromatography coupled with mass spectrometer, which mainly consists of eucalyptol, citronellal, and citral. Clinicohistopathological and electron microscopic studies demonstrated that the extract corrected blood cholesterol, LDL, HDL, and triglyceride levels similarly as simvastatin treatment in association with its antioxidative properties, as indicated by the levels of superoxide dismutase and malondialdehyde in serum and the increment of nuclear factor erythroid 2-related factor 2 levels in hepatocytes. Hepatitis was significantly less severe in rats fed the extract for 14 days than in simvastatin-treated rats. Regarding its immunomodulatory properties, the extract also accelerated hepatic resolution from steatohepatitis during hypercholesterolemia as indicated by the upregulation of vimentin, cytokeratin, and CD206+. Interestingly, liver mitochondria were also preserved in hypercholesterolemic rats treated with the extract in relation to their architecture and the expression of haloacid dehalogenase-like hydrolase domain-containing protein 3 as well as metabolic and energy regulators. Therefore, the study concluded that the water extract of kaffir lime leaves and the rhizomes of galangal and lemongrass has beneficial effects on blood cholesterol, the severity of steatohepatitis, and the maintenance of mitochondrial architecture via its antioxidative and immunomodulatory activities.

Regulatory effect of Phikud Navakot extract on HMG-CoA reductase and LDL-R: potential and alternate agents for lowering blood cholesterol.

BACKGROUND: For decades, various cardiovascular symptoms have been relieved by the use of Ya-Hom Navakot, which is a formulation comprising 54 herbal medicines. The Thailand Ministry of Public Health listed Ya-Hom Navakot's nine active principle and nomenclative herbal ingredients and termed them 'Phikud Navakot' (PN). Several reports have confirmed that PN has cardiovascular benefits similar to Ya-Hom Navakot. However, whether PN facilitates lipid-lowering activity remains unclear. METHODS: The present study investigated an in vitro model for examining the gene expression levels of 3-hydroxyl-3-methylglutaryl-CoA reductase (HMGCR) and low-density lipoprotein receptor (LDL-R) in HepG2 cells using qRT-PCR. The ethanol and water extractions of Ya-Hom Navakot, PN and Ya-Hom Navakot without PN were compared. RESULTS: One mg/ml of both NYEF and NYWF were found to significantly lower cholesterol by either the up-regulation of LDL-R or down-regulation of HMGCR compared with negative controls and 1 mg/ml simvastatin (p < 0.05). PNEF also up-regulated LDL-R gene expression, even more than NYEF (p < 0.05). In addition, the ethanol and water extracts of PN significantly down-regulated HMGCR gene expression compared with those of Ya-Hom Navakot without PN (p < 0.05). CONCLUSION: The use of Ya-Hom Navakot or PN may provide an alternative treatment to lower cholesterol through HMGCR gene inhibition and LDL-R gene enhancement.

Omeprazole preserves the RER in chief cells and enhances re-epithelialization of parietal cells with SOD and AQP-4 up-regulation in ethanol-induced gastritis rats.

Gastric mucosal cells, particularly parietal and chief cells, are usually affected by exogenous, and endogenous stimuli-induced gastritis. The integrity of these cells and their alterations are involved in the pathogenesis of numerous gastric disorders. Omeprazole, a gastric acid secretion blocker, is commonly used for gastrointestinal diseases due to its antioxidative stress and anti-inflammatory properties. Little is known regarding how omeprazole modulates the re-epithelialized effect on gastric mucosal cells associated with gastrointestinal disorders. The present study aimed to determine whether omeprazole attenuates parietal and chief cell damage in association with its antioxidative property. An in vivo ethanol-induced gastritis rat model was used. Histopathological, scanning and transmission electron microscopic, and immunohistochemical studies were performed. The results revealed that omeprazole improved the gastric mucosal surface, and reduced the severity of mucosal inflammation and hemorrhaging. Notably, ethanol-induced gastritis caused dysmorphic rough endoplasmic reticulum (RER) in chief cells, which was accompanied by mitochondrial swelling. This alteration was modulated by omeprazole due to its antioxidant effect characterized by upregulation of superoxide dismutase in gastric mucosal cells. In addition, expression of aquaporin-4 was increased in the omeprazole treatment group, which may be due to the expansion of regenerative parietal cells and acid suppression. The results of the present study suggest that omeprazole preserves the RER in chief cells and enhances parietal cell regeneration through its antioxidative property by exerting anti-inflammatory effects.