Liver and muscle health are intimately connected. Nutritional strategies that support liver detoxification are beneficial to muscle recovery. Computational–in silico–molecular systems’ biology analysis of supplementation of calcium and potassium glucarate salts and their metabolite D-glucaric acid (GA) reveals their positive effect on mitigation of liver detoxification via four specific molecular pathways: (1) ROS production, (2) deconjugation, (3) apoptosis of hepatocytes, and (4) β-glucuronidase synthesis. GA improves liver detoxification by downregulating hepatocyte apoptosis, reducing glucuronide deconjugates levels, reducing ROS production, and inhibiting β-Glucuronidase enzyme that reduces re-absorption of toxins in hepatocytes. Results from this in silico study provide an integrative molecular mechanistic systems explanation for the mitigation of liver toxicity by GA.

The quantification of synergistic effects of multi-combination compounds is critical in developing “cocktails” that are efficacious. In this research, a method for in silico modeling and the quantification of synergistic effects of multi-combination compounds is applied for assessing a combination of phytonutrients for joint pain. Joint pain is the most prominent and disabling symptom of arthritis. Arthritic pain leads to a reduced quality of life. This research explores the efficacy of a synergistic combination of two plant-based flavonoids—apigenin and hesperidin—on joint pain. The study employs computational systems biology: (1) to identify biomolecular mechanisms of joint pain; (2) to identify the specific effects of apigenin and hesperidin, individually and in combination, on the mechanisms of joint pain; and (3) to predict the quantitative effects of apigenin and hesperidin, individually and in combination, on joint pain and whether these combination effects are synergistic or additive. Four molecular pathways that are affected by apigenin and hesperidin include the following: (1) arachidonic acid metabolism, (2) PGE2 signaling, (3) COX-2 synthesis, and (4) oxidative stress. The combination of apigenin and hesperidin significantly lowered PGE2 production, CGRP production, TRVP-1 synthesis, COX-2 production, and reactive oxygen species (ROS) production. Our results indicate that the apigenin and hesperidin combination synergistically affected four of the five modalities to attenuate joint pain.

Aging results from gradual accumulation of damage to the cellular functions caused by biochemical processes such as oxidative stress, inflammation-driven prolonged cellular senescence state, immune system malfunction, psychological stress, and epigenetic changes due to exposure to environmental toxins. Plant-derived bioactive molecules have been shown to ameliorate the damage from oxidative stress. This research seeks to uncover the mechanisms of action of how phytochemicals from fruit/berry/vegetable (FBV) juice powder mitigate oxidative stress. The study uses a computational systems biology approach to (1) identify biomolecular pathways of oxidative stress; (2) identify phytochemicals from FBV juice powder and their specific action on oxidative stress mechanisms; and (3) quantitatively estimate the effects of FBV juice powder bioactive compounds on oxidative stress. The compounds in FBV affected two oxidative stress molecular pathways: (1) reactive oxygen species (ROS) production and (2) antioxidant enzyme production. Six bioactive compounds including cyanidin, delphinidin, ellagic acid, kaempherol, malvidin, and rutin in FBV significantly lowered production of ROS and increased the production of antioxidant enzymes such as catalase, heme oxygenase-1, superoxide dismutase, and glutathione peroxidase. FBV juice powder provides a combination of bioactive compounds that attenuate aging by affecting multiple pathways of oxidative stress.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrosing interstitial lung disease characterized by excessive extracellular matrix (ECM) accumulation, disruption of lung architecture, and progressive loss of pulmonary function. IPF is frequently accompanied by comorbid conditions that exacerbate disease progression and negatively impact prognosis. To address the biological complexity of IPF, this study presents a comprehensive molecular systems architecture that enables a system-level understanding of biomolecular interactions within the fibrotic lung microenvironment in response to external and physiological triggers. Methods: A literature search is conducted using the Medical Subject Headings (MeSH) keywords in PubMed and MEDLINE to identify relevant peer-reviewed articles published from April 2008 to June 2025, with Google Scholar used solely to retrieve full-text versions of articles identified through this search. The systems biology tool CytoSolve^® was used to perform the systematic review and to support the curation and development of the molecular systems architecture of IPF pathogenesis. Full-length articles that contained Medical Subject Headings keywords relevant to IPF pathogenesis were selected for a comprehensive review. A total of 150 studies published between April 2008 and June 2025 met the inclusion criteria and were included in the systematic analysis. This systematic review was not registered. Results: Findings were synthesized qualitatively into a multilayered molecular interactome rather than through statistical meta-analysis. The architecture integrates interactions across sixteen lung-associated cell types, including epithelial, endothelial, mesenchymal, immune, and stromal populations. Key external triggers—such as bleomycin (BLM), asbestos, silica, radiation, cigarette smoke, Herpes virus, and genetic mutations (SFTPC I73T), along with hypoxia associated with comorbidities—initiate coordinated cellular responses that converge on three fundamental pathological processes: inflammation, myofibroblast differentiation, and tissue remodeling. These interconnected processes collectively drive the initiation and progression of IPF. Conclusions: This molecular systems architecture unifies triggers, cellular components, molecular pathways, and biological processes into a multilayered framework for identifying therapeutic targets, biomarkers, and rational single- and combination-treatment strategies in IPF.