Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Alshehade, Salah Abdalrazak; Zarzour, Raghdaa Hamdan Al; Murugaiyah, Vikneswaran; Lim, Sharoen Yu Ming; El-Refae, Huda Ghaleb; Alshawsh, Mohammed Abdullah

doi:10.1016/j.jsps.2022.09.001

Cited by 7 publications

(6 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, since alterations in mitochondria can cause NAFLD, we examined the mitochondrial membrane potential as it is the central intermediate in oxidative energy metabolism and indicates the functional work of the mitochondria [ 50 ]. The highest concentration of all selected fractions showed a significant restoration of mitochondrial activity, which is supporting evidence for the antioxidant-based anti-NAFLD mechanism, especially when it correlates with high total phenolic content levels of the fractions recorded in this study and is consistent with the previous study results [ 51 , 52 ]. It has been established that phenolic compounds inhibit the radical processes of oxidation of substrates through the action of semiquinone present in the equilibrium system [ 53 ].…”

Section: Discussionsupporting

confidence: 92%

“…ALF.031997.06) conjugated to bovine serum albumin (BSA) in a ratio of 1:5 for a further 24 h. For all the tested conditions, media were starved without FBS (serum-free medium) and supplemented with 1% BSA. Post-steatotic cells were exposed to the treatment for further 24 h [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

“…875756-97-1) in PBS was added to each well and incubated for 15 min at 37 °C and 5% CO 2 in the dark. Then, cells were washed with PBS and imaged directly with a fluorescence microscope with excitation/emission maxima 488/550 nm for the Nile red and 350/461 nm for Hoechst 33342 [ 52 , 69 , 70 ]. The intracellular fat accumulation per cell was presented as a relative fold change as compared to the negative control (0.5 mM FA), which was computed in two steps.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic–Oleic Acid-Induced Steatosis in HepG2 Cells

et al. 2023

Self Cite

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease. Orthosiphon aristatus (Blume) Miq, a traditional plant in South Asia, has previously been shown to attenuate obesity and hyperglycaemic conditions. Eight weeks of feeding C57BL/6 mice with the standardized O. aristatus extract (400 mg/kg) inhibited the progression of NAFLD. Liver enzymes including alanine aminotransferase and aspartate transaminase were significantly reduced in treated mice by 74.2% ± 7.69 and 52.8% ± 7.83, respectively. Furthermore, the treated mice showed a reduction in serum levels of glucose (50% ± 5.71), insulin (70.2% ± 12.09), total cholesterol (27.5% ± 15.93), triglycerides (63.2% ± 16.5), low-density lipoprotein (62.5% ± 4.93) and atherogenic risk index relative to the negative control. Histologically, O. aristatus reversed hepatic fat accumulation and reduced NAFLD severity. Notably, our results showed the antioxidant activity of O. aristatus via increased superoxide dismutase activity and a reduction of hepatic malondialdehyde levels. In addition, the levels of serum pro-inflammatory mediators (IL-6 and TNFα) decreased, indicating anti-inflammatory activity. The aqueous, hydroethanolic and ethanolic fractions of O. aristatus extract significantly reduced intracellular fat accumulation in HepG2 cells that were treated with palmitic–oleic acid. Together, these findings suggest that antioxidant activities are the primary mechanism of action of O. aristatus underlying the anti-NAFLD effects.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic–Oleic Acid-Induced Steatosis in HepG2 Cells

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Compounds were docked flexibly using exhaustiveness set to 20. The accepted binding affinity scores cutoff was set to be ≤-6 (Alshehade et al, 2022).…”

Section: Validating and Filtering Predicted Targets Using Molecular D...mentioning

confidence: 99%

Innovative Piperidine-Catalyzation in Protecting Carbonyl Compounds with Implications for Angiogenesis and Inflammation

2024

J Angiotherapy

View full text Add to dashboard Cite

Introduction: This study explores the application of piperidine-catalyzed protection, an innovative technique, for safeguarding various carbonyl compounds functioning as acetals in a generic reaction. Specifically, we investigate the catalysis of 2-amino-1,3-propanediol-2-methyl with various aromatic aldehydes, leading to the production of cis and trans-5-methyl-2-(mono or di-substitutions-phenyl)-1,3-dioxane-5-amine. Methods: Identification of all newly formed products is achieved through the utilization of spectroscopic techniques, including IR, 1H-NMR, and 13C-NMR spectroscopy. Molecular interactions and potential therapeutic applications of compounds E1 and E2 are demonstrated with cAMP-specific phosphodiesterase (1zkl) and oxidized purine nucleoside triphosphate hydrolase (5ws7). Detailed structural analyses highlight specific hydrogen bonds, pi-pi stacked interactions, and alkyl contacts formed by these compounds with target proteins. A comprehensive bioinformatics approach involves GO enrichment, STRING protein-protein association networks, KEGG pathway analysis, and Reactome pathways to elucidate biological processes, molecular functions, and cellular components associated with the compounds. Results: Compounds E1 and E2 exhibit diverse enrichment profiles, suggesting their involvement in various signaling cascades, neurotransmission, immune responses, and cancer pathways. Comparative analysis of five compound pairs (A1/A2, B1/B2, C1/C2, D1/D2, E1/E2) reveals subtle distinctions in enrichment patterns, implying unique pharmacological advantages for each pair. Conclusion: This study introduces a separate investigation on piperidine-catalyzed protection of carbonyl groups in aldehydes, presenting a practical approach. Emphasizing the significance of understanding distinct biological signatures, our findings guide therapeutic applications and compound optimization, particularly in the context of anti-cancer therapeutics. The compounds show potential in modulating neuronal function, neurotransmission, cancer mechanisms, and immune responses, suggesting promising avenues for future research and development.

show abstract

“…AutoDock VINA (V. 1.1.2) was used to carry out molecular docking studies [15], aimed at understanding the potential interactions between SBE-ß-CDs and TQ, as well as telomerase and TQ. The 3D structures for SBE-ß-CDs, TQ, and telomerase were procured from PubChem and the Protein Data Bank (PDB) (ID: 2BCK), respectively.…”

Section: Molecular Dockingmentioning

confidence: 99%

Enhancing the Anti-Leukemic Potential of Thymoquinone/Sulfobutylether-β-cyclodextrin (SBE-β-CD) Inclusion Complexes

et al. 2023

Self Cite

View full text Add to dashboard Cite

Leukemia, a condition characterized by the abnormal proliferation of blood cells, poses significant challenges in cancer treatment. Thymoquinone (TQ), a bioactive compound derived from black seed, has demonstrated anticancer properties, including telomerase inhibition and the induction of apoptosis. However, TQ’s poor solubility and limited bioavailability hinder its clinical application. This study explored the use of Sulfobutylether-β-cyclodextrin (SBE-β-CD), a cyclodextrin derivative, to enhance the solubility and stability of TQ for leukemia treatment. SBE-β-CD offers low hemolytic activity and has been successfully employed in controlled drug release systems. The study investigated the formation of inclusion complexes between TQ and SBE-β-CD and evaluated their effects on leukemia cell growth and telomerase activity. The results indicated that the TQ/SBE-β-CD complex exhibited improved solubility and enhanced cytotoxic effects against K-562 leukemia cells compared to TQ alone, suggesting the potential of SBE-β-CD as a drug delivery system for TQ. The annexin V-FITC assay demonstrated increased apoptosis, while the qPCR quantification assay revealed reduced telomerase activity in leukemia cells treated with TQ/SBE-β-CD, supporting its anti-leukemic potential. The molecular docking analysis indicated a strong binding affinity between TQ and telomerase. However, further research is needed to optimize the apoptotic effects and minimize necrosis induction. In conclusion, TQ/SBE-β-CD shows promise as a novel strategy for leukemia treatment by inhibiting telomerase and enhancing the cytotoxic effects of TQ, offering a potential solution to overcome the limitations of TQ’s poor solubility and bioavailability.

show abstract

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Cited by 7 publications

References 84 publications

Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic–Oleic Acid-Induced Steatosis in HepG2 Cells

Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic–Oleic Acid-Induced Steatosis in HepG2 Cells

Innovative Piperidine-Catalyzation in Protecting Carbonyl Compounds with Implications for Angiogenesis and Inflammation

Enhancing the Anti-Leukemic Potential of Thymoquinone/Sulfobutylether-β-cyclodextrin (SBE-β-CD) Inclusion Complexes

Contact Info

Product

Resources

About