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.

Low-grade chronic inflammation (LGCI) is a strong and independent risk factor for many chronic diseases, like cardiovascular, musculoskeletal, metabolic, and neurological conditions. Dietary intervention studies have reported evidence for the role of plant-derived flavonoids in modulation of LGCI. This research explores the efficacy of Fruit/Berry/Vegetable (FBV) juice powder on LGCI. The study employs computational systems biology: 1) to identify biomolecular mechanisms of LGCI; 2) to identify the bioactive compounds of FBV juice powder and their specific effects on mechanisms of LGCI; and, 3) to predict the quantitative effects of those bioactive compounds on LGCI. Four molecular pathways that are affected by the compounds of FBV include: 1) TNF-α production; 2) CCL2 production; 3) IL-1β production; and 4) reactive oxygen species production. The bioactive compounds including luteolin, epicatechin, epigallocatechin gallate, lycopene, quercetin, vitamin A, vitamin C and vitamin E in FBV significantly lowered TNF-α production, CCL2 production, IL-1β production, and reactive oxygen species production. FBV provides a combination of active ingredients that synergistically affect multiple modalities of low grade chronic inflammation to help improve blood circulation and energy levels, and lower muscle soreness.

Green tea (Camellia sinensis) has bioactive compounds that have been shown to possess nutritive effects on various biomolecular processes such as immunomodulation. This research explores the immunomodulatory effects of green tea in reducing transplant rejection. The study employs computational systems biology: 1) to identify biomolecular mechanisms of immunomodulation in transplant rejection; 2) to identify the bioactive compounds of green tea and their specific effects on mechanisms of immunomodulation in transplant rejection; and, 3) to predict the quantitative effects of those bioactive compounds on immunomodulation in transplant rejection. Three bioactive compounds of green tea - epicatechin (EC), gallic acid (GA), and epigallocatechin gallate (EGCG), were identified for their potential effects on immunomodulation of transplant rejection. Of the three, EGCG was the only one determined to enhance anti-inflammatory activity by: 1) upregulating synthesis of HO-1 that is known to promote Treg and Th2 phenotypes associated with enabling transplant tolerance; and, 2) downregulating pro-inflammatory cytokines IL-2, IL-17, IFN-γ, TNF-α, NO, IL-6, and IL-1β that are known to promote Th1 and Th17 phenotypes associated with transplant rejection. To the best of our knowledge, this study provides the first molecular mechanistic understanding the clinical nutritive value of green tea, specifically the bioactive compound EGCG, in enabling transplant tolerance.

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.

A molecular systems architecture is presented for the neuromuscular junction (NMJ) in order to provide a framework for organizing complexity of biomolecular interactions in amyotrophic lateral sclerosis (ALS) using a systematic literature review process. ALS is a fatal motor neuron disease characterized by progressive degeneration of the upper and lower motor neurons that supply voluntary muscles. The neuromuscular junction contains cells such as upper and lower motor neurons, skeletal muscle cells, astrocytes, microglia, Schwann cells, and endothelial cells, which are implicated in pathogenesis of ALS. This molecular systems architecture provides a multi-layered understanding of the intra- and inter-cellular interactions in the ALS neuromuscular junction microenvironment, and may be utilized for target identification, discovery of single and combination therapeutics, and clinical strategies to treat ALS.

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.