Corydalmine

Corydalmine is a natural isoquinoline alkaloid predominantly found in plants of the genus Corydalis, possessing oral bioavailability and antifungal activity^[1]. Corydalmine alleviates neuropathic pain by inhibiting the NF-κB-dependent CXCL1/CXCR2 signaling pathway and inhibits fungal spore germination^[2,3]. Corydalmine is commonly used in the treatment of chronic pain conditions (such as bone cancer pain and neuropathic pain), as well as in studies on anti-inflammation and the inhibition of plant pathogenic fungi^[4,5].

In vitro, RAW 264.7 macrophages were pretreated with Corydalmine (15, 30, 60, 90μM) for 2h, followed by stimulation with lipopolysaccharide (LPS, 20ng/mL) for an additional 6h, and Corydalmine dose-dependently inhibited the LPS-induced mRNA expression levels of TNF-α and IL-6^[6]. Primary cultured mouse astrocytes were activated with TNF-α (10ng/mL) for 1h and then treated with Corydalmine (3, 10, 30μM) for 24h, which resulted in a concentration-dependent inhibition of TNF-α-induced Cx43 expression and ethidium bromide uptake^[7].

In vivo, Corydalmine (5, 10, 20mg/kg; once daily) was administered intragastrically for 9 consecutive days to mice with neuropathic cancer pain induced by S180 sarcoma cell inoculation, resulting in a dose-dependent and significant inhibition of astrocyte and microglial activation in the spinal dorsal horn^[8]. In a mouse model of vincristine-induced neuropathic pain, intragastric administration of Corydalmine (5, 10, 20mg/kg; once daily) for 9 consecutive days dose-dependently promoted the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) from the cytoplasm to the nucleus^[7].

References:
[1] HE X, ZENG Y, JIANG W. Eleven isoquinoline alkaloids on inhibiting tissue factor activity: structure-activity relationships and molecular docking[J]. Zeitschrift für Naturforschung C, 2021, 76(1-2): 11-19.
[2] ZHOU L, HU Y, LI C, et al. Levo-corydalmine alleviates vincristine-induced neuropathic pain in mice by inhibiting an NF-kappa B-dependent CXCL1/CXCR2 signaling pathway[J]. Neuropharmacology, 2018, 135: 34-47.
[3] BASHA S A, JHA R N, PANDEY V B, et al. Effect of 1-corydalmine, an alkaloid isolated from Corydalis chaerophylla roots on spore germination of some fungi[J]. Mycobiology, 2007, 35(2): 69-71.
[4] TANG X, DI X, ZHONG Z, et al. In vitro metabolism of l-corydalmine, a potent analgesic drug, in human, cynomolgus monkey, beagle dog, rat and mouse liver microsomes[J]. Journal of Pharmaceutical and Biomedical Analysis, 2016, 128: 98-105.
[5] DAI W L, BAO Y N, FAN J F, et al. Levo-corydalmine attenuates microglia activation and neuropathic pain by suppressing ASK1-p38 MAPK/NF-κB signaling pathways in rat spinal cord[J]. Regional Anesthesia & Pain Medicine, 2020, 45(3): 219-229.
[6] KONG X, CHEN Z, XIA Y, et al. Dehydrocorydaline accounts the majority of anti-inflammatory property of Corydalis Rhizoma in cultured macrophage[J]. Evidence-Based Complementary and Alternative Medicine, 2020, 2020(1): 4181696.
[7] ZHOU L, AO L, YAN Y, et al. Levo-corydalmine attenuates vincristine-induced neuropathic pain in mice by upregulating the Nrf2/HO-1/CO pathway to inhibit connexin 43 expression[J]. Neurotherapeutics, 2020, 17(1): 340-355.
[8] HU Y, KODITHUWAKKU N D, ZHOU L, et al. Levo-corydalmine alleviates neuropathic cancer pain induced by tumor compression via the CCL2/CCR2 pathway[J]. Molecules, 2017, 22(6): 937.

Corydalmine是一种主要存在于Corydalis菌属的，具有口服和抗菌活性的天然异喹啉生物碱^[1]。Corydalmine通过抑制NF-κB依赖的CXCL1/CXCR2信号通路缓解神经性疼痛，并可抑制真菌孢子的萌发^[2,3]。Corydalmine通常被用于慢性疼痛的治疗（如骨癌痛和神经病性痛），以及抗炎和抑制植物致病真菌的研究^[4,5]。

在体外，Corydalmine（15, 30, 60, 90μM）预处理RAW 264.7巨噬细胞2h，再加入脂多糖（LPS, 20ng/mL）继续处理6h，可剂量依赖性地抑制由LPS诱导的细胞内TNF-α和IL-6的mRNA表达水平^[6]。原代培养的小鼠星形胶质细胞用TNF-α（10ng/mL）预处理1h激活，再加入Corydalmine（3, 10, 30μM）共孵育24h，可浓度依赖性地抑制TNF-α诱导的Cx43表达，并减少溴化乙锭的摄取^[7]。

在体内，Corydalmine（5, 10, 20mg/kg; once daily）通过灌胃给药S180肉瘤细胞接种诱导的神经病理性癌痛模型小鼠连续9天，可剂量依赖性且显著地抑制小鼠脊髓背角中星形胶质细胞和小胶质细胞的活化^[8]。Corydalmine（5, 10, 20mg/kg; once daily）通过灌胃给药vincristine诱导的神经病理性疼痛模型小鼠连续9天，可剂量依赖性地促进核因子E2相关因子2（Nrf2）从细胞质向细胞核转位^[7]。