Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the main active ingredients for the RSF and FC herbal pair. We demonstrate that the RSF–FC herbal pair can be elucidated by mining the chemical structures of compounds derived from RSF and FC. Based on chemical structure data, the putative targets for RSF and FC were predicted. Additional putative targets that interact with the anti-pruritus targets were derived by mapping the putative targets onto a PPI network. By examining the annotations of these proteins, we conclude that (1) RSF’s active compounds are mainly alkaloids and flavonoids. The representative putative targets of the alkaloids are inflammation-related proteins (MAPK14, PTGS2, PTGS2, and F2) and pruritus-related proteins (HRH1, TRPA1, HTR3A, and HTR6). The representative putative targets of the flavonoids are inflammation-related proteins (TNF, NF-κB, F2, PTGS2, and PTGS2) and pruritus-related proteins (NR3C1 and IL2). (2) FC’s active compounds are mainly coumarins. Their representative putative targets are CNS-related proteins (AChE and OPRK1) and inflammation-related proteins (PDE4D, TLR9, and NF-κB). (3) Both RSF and FC display anti-inflammatory effects, though they exhibit their anti-pruritus effects in different ways. Their synergy shows that RSF regulates inflammation-related pruritus and FC regulates CNS-related pruritus.

Traditional Chinese medicine (TCM) has been widely used and proven effective in long term clinical practice. However, the molecular mechanism of action for many TCMs remains unclear due to the complexity of many ingredients and their interactions with biological receptors. This is one of the major roadblocks in TCM modernization. In order to solve this problem, we have developed TCMAnalyzer, which is a free web-based toolkit allowing a user to (1) identify the potential compounds that are responsible for the bioactivities for a TCM herb through scaffold-activity relation searches using structural search techniques, (2) investigate the molecular mechanism of action for a TCM herb at the systemic level, and (3) explore the potentially targeted bioactive herbs. The toolkit can result in TCM networks that demonstrate the relations among natural product molecules (small molecular ligands), putative protein targets, pathways, and diseases. These networks are graphically depicted to reveal the mechanism of actions for a TCM herb or to identify new molecular scaffolds for new chemotherapies. TCMAnalyzer is freely available at http://www.rcdd.org.cn/tcmanalyzer .

S1S1 Changes in measured RO2 and closed-shell products as a function of the reacted α-pinene.The changes of selected RO2 and the corresponding closed-shell monomers and dimers as a function of the reacted α-pinene are consistent with previous studies (Figure S7) (Zhao et al., 2018). The RO2 concentration increases rapidly when the reacted α-pinene is relatively low, and the increasing rate slows down due to the elevated removal rate of RO2 via cross-reactions at higher reacted α-pinene (> 20 ppb). The dimers exhibit opposite trends with RO2. As the reacted α-pinene increases, the increasing rates of the dimers become slightly higher due to the promoted RO2 cross-reactions. As for the HOM monomers, their concentrations basically show linear correlations with increasing reacted α-pinene. S2Table S1 Summary of experimental conditions of α-pinene ozonolysis with the addition of NO2.

Abstract. Acylperoxy radicals (RO2) are key intermediates in atmospheric oxidation of organic compounds and different from the general alkyl RO2 radicals in reactivity. However, direct probing of the molecular identities and chemistry of acyl RO2 remains quite limited. Here, we report a combined experimental and kinetic modelling study of the composition and formation mechanisms of acyl RO2, as well as their contributions to the formation of highly oxygenated organic molecules (HOMs) during ozonolysis of α-pinene. We find that acyl RO2 radicals account for 67 %, 94 %, and 32 % of the highly oxygenated C7, C8, and C9 RO2, respectively, but only a few percent of C10 RO2. The formation pathway of acyl RO2 species depends on their oxygenation level. The highly oxygenated acyl RO2 (oxygen atom number ≥ 6) are mainly formed by the intramolecular aldehydic H-shift (i.e., autoxidation) of RO2, while the less oxygenated acyl RO2 (oxygen atom number < 6) are basically derived from the C-C bond cleavage of alkoxy (RO) radicals containing an α-ketone group or the intramolecular H-shift of RO containing an aldehyde group. The acyl RO2-involved reactions explain 50–90 % of C7 and C8 closed-shell HOMs and 14 % of C10 HOMs, respectively. For C9 HOMs, this contribution can be up to 30 %–60 %. In addition, acyl RO2 contribute to 50 %–95 % of C14–C18 HOM dimer formation. Because of the generally fast reaction kinetics of acyl RO2, the acyl RO2 + alkyl RO2 reactions seem to outcompete the alkyl RO2 + alkyl RO2 pathways, thereby affecting the fate of alkyl RO2 and HOM formation. Our study sheds lights on the detailed formation pathways of the monoterpene-derived acyl RO2 and their contributions to HOM formation, which will help to understand the oxidation chemistry of monoterpenes and sources of low-volatility organic compounds capable of driving particle formation and growth in the atmosphere.