神經系統的炎症可以由多種因素導致，常見的有病毒或細菌感染、藥物或有毒物質、自身免疫相關或特發性（原因不明的，如多發性硬化等）。神經系統的炎症不光導致感覺和運動異常，也可以表現為精神和行為障礙，如癡呆、精神分裂症等，因此，它與許多神經系統疾病密切相關，例如阿爾茨海默氏病（老年癡呆） 、帕金森氏病、多發性硬化等。

神經炎症與抑鬱症和許多其他神經精神疾病密切相關。雖然針對炎症介質的神經系統藥物表現出一定的療效，但它面臨著一些挑戰，特別是藥物輸送和安全問題。最新的研究表明，從五加科植物中提取的人參達瑪烷皂苷Rg1能夠減輕神經系統炎症導致的精神行為障礙。

這個研究發現，外周的免疫調節劑可以有效地減輕神經發炎引起的異常行為，而這種免疫調節劑不需要滲透入腦（直接在外周血發揮作用）。在腦脂多醣（LPS）刺激的大鼠模型中，科學家也證實，一個行之有效的消炎製劑- 人參達瑪烷皂苷Rg1（達瑪烷皂苷Rg1），無法穿透血腦屏障而進入大腦發揮作用。但有趣的是，只在外周血液和組織發揮免疫調節作用的達瑪烷皂苷Rg1能有效地減輕受試大鼠的體重減輕，厭食症，抑鬱症樣行為，以及腦神經化學物質的異常。在外圍神經免疫介質的生化分析表明，人參達瑪烷皂苷Rg1可以減輕下丘腦–垂體–腎上腺軸的調節失控，並且選擇性地減輕血液循環中白細胞介素-6水平的上升。與此相伴的是大腦內小膠質細胞活化的抑制，促炎介質和神經毒性物質的減輕。

總而言之，該研究表明，針對外周免疫系統的治療可作為一種新方法，用於治療神經炎症引起的神經精神障礙。例如，該研究為外周免疫調節劑達瑪烷皂苷Rg1用於對抗精神障礙提供了依據。

原文發表於：Neuroscience. 2013 Oct 23;256C:210-222

Peripheral immunomodulation with ginsenoside Rg1 ameliorates neuroinflammation-induced behavioral deficits in rats.

摘要：Neuroinflammatory disturbances have been closely associated with depression and many other neuropsychiatric diseases. Although targeting neuroinflammatory mediators with centrally acting drugs has shown certain promise, its translation is faced with several challenges especially drug delivery and safety concerns. Here, we report that neuroinflammation-induced behavioral abnormality could be effectively attenuated with immunomodulatory agents that need not to gain brain penetration. In a rat model with intracerebral lipopolysaccharide (LPS) challenge, we validated that ginsenoside Rg1 ( Rg1 ), a well-established anti-inflammatory agent, was unable to produce a direct action in the brain. Interestingly, peripherally restricted Rg1 could effectively attenuate the weight loss, anorexic- and depressive-like behavior as well as neurochemical disturbances associated with central LPS challenge. Biochemical assay of neuroimmune mediators in the periphery revealed that Rg1 could mitigate the deregulation of the hypothalamic-pituitary-adrenal axis and selectively blunt the increase in circulating interleukin-6 levels. Furthermore, these peripheral regulatory effects were accompanied by dampened microglial activation, mitigated expression of pro-inflammatory mediators and neurotoxic species in the central compartment. Taken together, our work suggested that targeting the peripheral immune system may serve as a novel therapeutic approach to neuroinflammation-induced neuropsychiatric disorders. Moreover, our findings provided the rationale for employing peripherally active agents like Rg1 to combat mental disturbances.