Abstract
Neuroinflammation is characterized by the elaborated inflammatory response repertoire of central nervous system tissue. The limitations of the current treatments for neuroinflammation are well-known side effects in the clinical trials of monotherapy. Drug combination therapies are promising strategies to overcome the compensatory mechanisms and off-target effects. However, discovery of synergistic drug combinations from herb medicines is rare. Encouraged by the successfully applied cases we move on to investigate the effective drug combinations based on system pharmacology among compounds from Cistanche tubulosa (SCHENK) R. WIGHT. Firstly, 63 potential bioactive compounds, the related 133 direct and indirect targets are screened out by Drug-likeness evaluation combined with drug targeting process. Secondly, Compound-Target network is built to acquire the data set for predicting drug combinations. We list the top 10 drug combinations which are employed by the algorithm Probability Ensemble Approach (PEA), and Compound-Target-Pathway network is then constructed by the 12 compounds of the combinations, targets, and pathways to unearth the corresponding pharmacological actions. Finally, an integrating pathway approach is developed to elucidate the therapeutic effects of the herb in different pathological features-relevant biological processes. Overall, the method may provide a productive avenue for developing drug combination therapeutics.
Highlights
Neurogenic neuroinflammation is defined as orchestrated actions of innate and adaptive immune cells, vascular cells and neurons triggered by pathological states and enhanced neuronal activity in the central nervous system (CNS)
To get the targets related to neuroinflammation we firstly achieve the ingredients in Cistanche tubulosa (SCHENK) R
Current treatments for neuroinflammatory are monotherapies mostly, limited by well-known side effects as we know, COX-2 inhibitors may lead cardiovascular defects responded to long-term treatment, and TNF-targeted treatment could cause infection through immunosuppression[62]
Summary
Neurogenic neuroinflammation is defined as orchestrated actions of innate and adaptive immune cells, vascular cells and neurons triggered by pathological states and enhanced neuronal activity in the central nervous system (CNS). Combination or multicomponent therapy could fulfill the above requirements, in which two or more drugs are used together[5], with the listed advantages: higher efficacy, minimal cross-resistance, low dose while fewer side effects, and less toxicity when compared to single-drug agent[6]. It has been used in the treatment of complex diseases[7,8] for nearly 30 years. We found two representative herbs Lonicera japonica and Fructus Forsythiae show synergistic effects on influenza or inflammation[23], and compounds rutin and amentoflavone present synergistic effects in preventing depression[24]
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