Table 2.

Main anti-neuroinflammatory effects of substances derived from S. chinensis, E. senticosus, R. rosea, and W. somnifera found in studies (see text above and references for further details).

Observed Effect	Substance	Assay/Model	Ref.
↓TNF-α	schisandrin A schisandrin B (gomisin N) schisandrin C schisandrol B (gomisin A) Schisandra lignans SCP-2 Schisandra essential oil E. senticosus extract salidroside R. rosea extract, rosin, rosarin, salidroside R. rosea extract withanone withanolide A W. somnifera extract	BV-2 microglial cells, mouse primary microglia micorglia–neuron cocultures BV-2 microglial cells forced swim test (amygdala, hypothalamus) BV-2 microglial cells N9 microglial cells forced swim test in mice (hippocampal tissue) LPS-injected mice Aβ1-42-induced dementia in rats transient middle cerebral artery occlusion in rats rats with induced ischemic strokeBV-2 microglial cells LPS-injected mice BV-2 cells streptozotocin-induced dementia in rats pilocarpine-induced status epilepticus in mice AlCl3-induced brain damage in rats (hippocamups, cortex) thioacetamice-induced hepatic encephalopathy in mice	[53] [103] [54] [55] [51] [62] [61] [63] [65] [75] [76] [85] [80] [81] [90] [91] [89] [94]
↓IL-1β	schisandrin B schisandrol B (gomisin A) Schisandra lignans Schisandra essential oil E. senticosus extract R. rosea extract, rosin, rosarin, salidroside withanone withanolide A W. somnifera extract	micorglia-neuron cocultures BV-2 microglial cells forced swim test (amygdala, hypothalamus) subarachnoid hemorrhage in rats N9 microglial cells BV-2 microglial cells forced swim test in mice (hippocamp tissue) Aβ1-42-induced dementia in rats rats with induced ischemic stroke BV-2 microglial cells streptozotocin-induced dementia in rats pilocarpine-induced status epilepticus in mice transgenic mice with ALS	[103] [54] [55] [57] [62] [61] [65] [76] [80] [90] [91] [101]
↓IL-6	schisandrin A schisandrin B schisandrin C schisandrol B (gomisin A) Schisandra lignans E. senticosus extract salidroside R. rosea extract, rosin, rosarin, salidroside R. rosea extract R. rosea extract (standardized for salidroside) withanone W. somnifera extract	BV-2 microglial cells, mouse primary microglia micorglia–neuron cocultures BV-2 microglial cells forced swim test (amygdala, hypothalamus) BV-2 microglial cells N9 microglial cells forced swim test in mice (hippocampal tissue) rats with induced ischemic stroke transient middle cerebral artery occlusion in rats BV-2 microglial cells BV-2 cells autoimmune encephalomyelitis in mice streptozotocin-induced dementia in rats transgenic mice with ALS	[53] [103] [54] [55] [51] [62] [61] [76] [85] [80] [81] [82] [90] [101]
↓IFN-γ	R. rosea extract (standardized for salidroside) withanone W. somnifera extract	autoimmune encephalomyelitis in mice streptozotocin-induced dementia in rats transgenic mice with ALS	[82] [90] [101]
↓iNOS	schisandrin B schisandrin C Schisandra lignans R. rosea extract, rosin, rosarin, salidroside E. senticosus extract	BV-2 microglial cells forced swim test (amygdala, hypothalamus) BV-2 microglial cells forced swim test in mice (hippocampal tissue) BV-2 microglial cells rats with induced ischemic stroke	[54] [55] [51] [61] [80] [75]
↓NO	schisandrin A schisandrin B withanolide A withaferin A W. somnifera extract	BV-2 microglial cells, mouse primary microglia micorglia–neuron cocultures BV-2 microglial cells BV-2 microglial cells BV-2 microglial cells	[53] [103] [98] [98] [98]
↓COX-2	schisandrin B schisandrin C Schisandra lignans E. senticosus extract	BV-2 microglial cells forced swim test (amygdala, hypothalamus) BV-2 microglial cells forced swim test in mice (hippocamp) rats with induced global cerebral ischemia rats with induced ischemic stroke	[54] [55] [51] [61] [74] [75]
↓PGE2	schisandrin B schisandrin C	micorglia–neuron cocultures BV-2 microglial cells BV-2 microglial cells	[103] [54] [51]
↓NF-κB	schisandrin A schisandrin B schisandrin C schisandrol B (gomisin A) SCP-2 salidroside R. rosea extract withanolide A withaferin A W. somnifera extract	BV-2 microglial cells, mouse primary microglia micorglia–neuron cocultures BV-2 microglial cells middle cerebral artery occlusion and reperfusion in rats subarachnoid hemorrhage in rats BV-2 microglial cells N9 microglial cells LPS-injected mice transient middle cerebral artery occlusion in rats LPS-injected rats BV-2 cells AD in mice transgenic mice with FTLD thioacetamice-induced hepatic encephalopathy LPS-injected rats transgenic mice with ALS	[53] [103] [54] [56] [57] [51] [62] [63] [85] [86] [81] [92] [101] [94] [99] [101]
↓MAPK	schisandrin C SCP-2 R. rosea extract R. rosea extract W. somnifera extract	BV-2 microglial cells LPS-injected mice LPS-injected mice BV-2 cells thioacetamice-induced hepatic encephalopathy LPS-injected rats	[51] [63] [80] [81] [94] [99]
↓JAK/STAT activation	schisandrin A schisandrin C Schisandra lignans micrandilactone C R. rosea extract (standardized for salidroside)	BV-2 microglial cells, mouse primary microglia BV-2 microglial cells forced swim test in mice (hippocampal tissue) 3-NPA-induced HD in mice autoimmune encephalomyelitis in mice	[53] [51] [61] [66] [82]
↓inflammasome formation	schisandrin B withanolide A	subarachnoid hemorrhage in rats AD in mice	[57] [92]
↓MCP-1	withanone W. somnifera extract	streptozotocin-induced dementia in rats transgenic mice with ALS	[90] [101]
↑Nrf-2	schisandrin C salidroside withanolide A withaferin A W. somnifera extract	BV-2 microglial cells transient middle cerebral artery occlusion in rats LPS-injected rats BV-2 microglial cells BV-2 microglial cells thioacetamice-induced hepatic encephalopathy BV-2 microglial cells	[51] [85] [86] [98 [98] [94] [98]
↑HO-1	salidroside withanolide A withaferin A W. somnifera extract	transient middle cerebral artery occlusion in rats LPS-injected rats BV-2 microglial cells BV-2 microglial cells thioacetamice-induced hepatic encephalopathy BV-2 microglial cells	[85] [87] [98] [98] [94] [98]
↑IL-4	E. senticosus extract R. rosea extract (standardized for salidroside) W. somnifera extract	rats with induced ischemic stroke autoimmune encephalomyelitis in mice transgenic mice with ALS	[75] [82] [101]
↑IL-10	E. senticosus extract	rats with induced ischemic stroke	[75]

↑ increase, ↓ decrease; S. chinensis—Schisandra chinensis; E. senticosus—Eleuterococcus senticosus; R. rosea—Rhodiola rosea; W. somnifera—Withania somnifera; 3-NPA—3-nitropropionic acid; AD—Alzheimer’s disease; COX-2—cyclooxygenase-2; HO-1—hemoxygenase-1; IL—interleukin; IFN-γ—interferon-γ; iNOS—inducible NO synthase; JAK/STAT—prostaglandin E₂; MAPK—mitogen-activated protein kinase; MCP-1—monocyte chemoattractant protein-1; NF-κB—nuclear factor kappa-light-chain-enhancer of activated B cells; NO—nitrogen oxide; Nrf-2—nuclear factor erythroid 2-related factor 2; PGE₂—prostaglandin E₂; PI3K/Akt—phosphatidylinositol-3 kinase/protein kinase B; SCP—Schisandra crude polysaccharide; SCP-2—purified fraction of SCP; TNF-α—tumor necrosis factor α.