Shoaib Rana Muhammad, Ahsan Muhammad Zaeem, Akhtar Usman, Ahmad Khalil Ali, Ali Usman, Deng Men-Yan, Li Xin-Yan, Wang Yong-Xiang
King's Lab, Shanghai Jiao Tong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China.
Faculty of Pharmacy, Superior University, Lahore, Punjab, Pakistan.
Neurosci Res. 2023 Mar;188:75-87. doi: 10.1016/j.neures.2022.11.003. Epub 2022 Nov 8.
Panax notoginseng (Chinese ginseng, Sanqi), one of the major ginseng species, has been traditionally used to alleviate different types of chronic pain. The raw P. notoginseng powder is commonly available in China as a non-prescription drug to treat various aliments including arthritic pain. However, strong scientific evidence is needed to illustrate its pain antihypersensitive effects, effective ingredients and mechanism of action. The oral P. notoginseng powder dose-dependently alleviated formalin-induced tonic hyperalgesia, and its total ginsenosides remarkably inhibited neuropathic pain hypersensitivity. Ginsenoside Rb1, the most abundant ginsenoside of P. notoginseng, dose-dependently produced neuropathic pain antihypersensitivity. Conversely, ginsenosides Rg1, Re and notoginseng R1, the other major saponins from P. notoginseng, failed to inhibit formalin-induced tonic pain or mechanical allodynia in neuropathic pain. Ginsenoside Rb1 metabolites ginsenosides Rg3, Compound-K and protopanaxadiol also had similar antineuropathic pain efficacy to ginsenoside Rb1. Additionally, intrathecal ginsenoside Rb1 specifically stimulated dynorphin A expression which was colocalized with microglia but not neurons or astrocytes in the spinal dorsal horn and primary cultured cells. Pretreatment with microglial metabolic inhibitor minocycline, dynorphin A antiserum and specific κ-opioid receptor antagonist GNTI completely blocked Rb1-induced mechanical antiallodynia in neuropathic pain. Furthermore, the specific glucocorticoid receptor (GR) antagonist Dex-21-mesylate (but not GPR30 estrogen receptor antagonist G15) also entirely attenuated ginsenoside Rb1-related antineuropathic pain effects. All these results, for the first time, show that P. notoginseng alleviates neuropathic pain and ginsenoside Rb1 is its principal effective ingredient. Furthermore, ginsenoside Rb1 inhibits neuropathic pain by stimulation of spinal microglial dynorphin A expression following GR activation.
三七（中国人参、三七）是主要的人参品种之一，传统上用于缓解不同类型的慢性疼痛。生三七粉在中国通常作为非处方药出售，用于治疗包括关节炎疼痛在内的各种疾病。然而，需要强有力的科学证据来阐明其抗疼痛超敏反应的作用、有效成分和作用机制。口服三七粉可剂量依赖性地减轻福尔马林诱导的强直性痛觉过敏，其总皂苷能显著抑制神经性疼痛超敏反应。人参皂苷Rb1是三七中含量最丰富的人参皂苷，能剂量依赖性地产生神经性疼痛抗超敏反应。相反，人参皂苷Rg1、Re和三七皂苷R1，三七中的其他主要皂苷，未能抑制福尔马林诱导的强直性疼痛或神经性疼痛中的机械性异常性疼痛。人参皂苷Rb1的代谢产物人参皂苷Rg3、Compound-K和原人参二醇也具有与人参皂苷Rb1相似的抗神经性疼痛功效。此外，鞘内注射人参皂苷Rb1可特异性刺激强啡肽A的表达，强啡肽A与脊髓背角和原代培养细胞中的小胶质细胞共定位，但不与神经元或星形胶质细胞共定位。用小胶质细胞代谢抑制剂米诺环素、强啡肽A抗血清和特异性κ-阿片受体拮抗剂GNTI预处理可完全阻断Rb1诱导的神经性疼痛中的机械性抗异常性疼痛。此外，特异性糖皮质激素受体（GR）拮抗剂甲磺酸地塞米松-21（而非GPR30雌激素受体拮抗剂G15）也完全减弱了人参皂苷Rb1相关的抗神经性疼痛作用。所有这些结果首次表明，三七可减轻神经性疼痛，人参皂苷Rb1是其主要有效成分。此外，人参皂苷Rb1通过激活GR后刺激脊髓小胶质细胞强啡肽A的表达来抑制神经性疼痛。
