Table 2.

Phytochemicals along with their diverse mechanistic insights against neuroinflammation in ALS.

Phytochemical constituent	Study type Cellular/Animal/clinical	Description of Study	Mechanism	Refs.
Celastrol (8)	G93A SOD1 transgenic mouse model of ALS	Transgenic mice were transfected with NSC34 cells and then treated with hydrogen peroxide and celastrol at different doses	Activation in MEK/ERK and PI3K/Akt pathway	[82, 113, 114]
	Transgenic mouse model of ALS	Celastrol was administered to the mice at 30 days of age, and reduction in body weight, improvement in motor function along with delayed onset of ALS was achieved.	Suppresses the TNF-α and iNOS expression Downregulated the expression of CD40
	SH-SY5Y neuronal cell model	There was Increased induction of Heat shock proteins (HSPs) after Co-application of celastrol and arimoclomol	Activation of HSPF1.
Resveratrol (9)	Rat cortical neuron cell model	Cell survival increased up to 75 % on the application of RSV with protection against neurodegeneration	Inhibits the release of pro-inflammatory cytokines	[88, 91, 93, 115-118]
	VSC 4.1 hybrid cell line	Mutant SOD1 expression was induced in the cell line, and on administration of RSV, the cell survival was enhanced with respect to dose, and at highest dose of RSV, cell survival was fully restored.
	Transgenic SOD mice model	Intraperitoneal administration of RSV led to a significant reduction in motor neuron death along with increased survival rates
Curcumin (10)	Motor neuron Cell model	Cell line transfected with mutant Q331K and wild TDP43 was treated with curcumin that led to altered membrane permeability of neurons.	Upregulates the expression of (Nrf-2) and (HO-1)	[39, 99, 119]
	Double-blind therapeutic trial for 42 patients	Patients were divided into Group A & B. group A received a placebo for three months followed by curcumin for other three months, while Group B received curcumin for six months
Isorhynchophylline (IRN) (11)	BM-hMSCs model	Regulation of the intracellular pluripotency mechanisms was examined.	Regulation of mitochondrial function, NMDA subunit, FGFβ levels, BDNF, OXTR, ATP, BM-MSC proliferation and differentiation.	[101, 102, 120, 121]
	Mouse N9 microglial cells	Inhibitory tendencies of RIN and IRN against cytokines and NO were a point of focus	Inhibits the pro-inflammatory cytokines release in LPS stimulated microglial cells
Obovatol (12)	Microglia BV-2 cell line	LPS induced stimulation was carried out in the cell line to mark changes with respect to NO, cytokines, along with activation of signalling cascades.	Suppresses the release of NO and iNOS in microglial cells	[104, 122, 123]
Paeonol PAE (13)	N9 microglia cell model	Role of PAE in the production of pro-inflammatory markers in LPS stimulated microglia cells and proteins formed in immune signalling cascade were observed	Downregulates the COX-2 and iNOS expression. Involvement of TLR4 signalling pathway to reduce the expression of TRAF6, MAPK molecules, etc.	[107, 109]
Wogonin (14)	SH-SY5Y cells	Aβ changes were observed in the cell line with treatment by wogonin.	GSK3β inhibition via the mediation of mTOR signalling pathway	[110, 124, 125]
	Microglia cell	Lps stimulated microglial cells were subjected to treatment to monitor changes with regard to TNF, NO and IL-6.	Inhibiting the NO, TNF-α, and IL-6production.