Lv, Zhangming; Shen, Jiayun; Gao, Xuejiao; Ruan, Yonglan; Ling, Jinying; Sun, Rongwei; Dai, Jingya; Fan, Haizhen; Cheng, Xiaolan; Cao, Peng published the artcile< Herbal formula Huangqi Guizhi Wuwu decoction attenuates paclitaxel-related neurotoxicity via inhibition of inflammation and oxidative stress>, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is Huangqi Guizhi Wuwu neuroprotective agent peripheral neuropathy; Huangqi Guizhi Wuwu decoction; Inflammation; Network pharmacology; Oxidative stress; Paclitaxel; Peripheral neuropathy.
Paclitaxel-induced peripheral neuropathy (PIPN) is a challenging clin. problem during chemotherapy. Our previous work found that herbal formula Huangqi Guizhi Wuwu decoction (HGWD) could reduce oxaliplatin-induced neurotoxicity. However, its effect on PIPN remains unknown. In this study, we aim to investigate the therapeutic effect and the underlying mechanisms of HGWD against PIPN with pharmacol. experiment and network pharmacol. Male Wistar rats were used to establish an animal model of PIPN and treated with different doses of HGWD for 3 wk. Mech. allodynia, thermal hyperalgesia and body weight were measured to evaluate the therapeutic effect of HGWD on PIPN rats. On the day of the sacrifice, blood, DRGs, sciatic nerve, and hind-paw intra-plantar skins were collected to assess neuroprotective effect of HGWD on PIPN. Next, network pharmacol. was performed to decipher the potential active components and mol. mechanisms of HGWD, as were further verified by western blotting analyses in PIPN rats. Finally, the effect of HGWD on the chemotherapeutic activity of paclitaxel was evaluated in vitro and in vivo. In rats with PIPN, HGWD reversed mech. allodynia, thermal hyperalgesia, and ameliorated neuronal damage. Moreover, HGWD significantly increased the level of nerve growth factor, dramatically reduced IL-1β, IL-6, TNF-α levels and oxidative stress. Network pharmacol. anal. revealed 30 active ingredients in HGWD and 158 candidate targets. Integrated pathway anal. identified PI3K/Akt and toll-like receptor as two main pathways responsible for the neuroprotective effect of HGWD. Further exptl. validation demonstrated that HGWD expectedly inhibited the protein expression of TLR4, MyD88, IKKα, and p-NF-κB, and promoted PI3K, p-Akt, Nrf2, and HO-1 level in dorsal root ganglia. Last but not least, HGWD did not interfere with the antitumor activity of paclitaxel both in in vitro and in vivo models. These combined data showed that HGWD could inhibit paclitaxel-evoked inflammatory and oxidative responses in peripheral nervous system viaTLR4/NF-κB and PI3K/Akt-Nrf2 pathways involvement. The neuroprotective property of HGWD on PIPN provides fundamental support to the potential application of HGWD for counteracting the side effects of paclitaxel during chemotherapy.
Chinese Medicine (London, United Kingdom) published new progress about Body weight. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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