. 2023 Nov 13;17:3295–3323. doi: 10.2147/DDDT.S380612

Table 2.

The Mechanisms of Natural Products in the Deposition of Tau Protein Hyperphosphorylation

Natural Products/Extracts	Natural Product/Extract Source	Molecular Formula	Molecular Weight	Chemical Structure	CAS No.	Animal Models	Mechanism of Action/Effectiveness	References
Ginsenoside Rg1	Panax ginseng C. A. Meyer	C₄₂H₇₂O₁₄	801.01		22,427–39-0	OA induced Tau hyperphosphorylation in rats cultured brain slices method	Reduced the expression of P-tau and PKA, and attenuated the OA-induced Tau protein hyperphosphorylation.	[100]
Panax notoginseng saponin Rg1	Panax pseudo-ginseng Wall. var. notoginseng (Burkill)Hoo & Tseng	–	–	–	–	The left ventricle injection of Aβ25-35 in SD rats.	The expression of tau protein phosphorylation at Thr231 in the DG, CA1, and CA3 regions of the hippocampus was reduced,	[101]
Curcumin	Curcuma longa Linn.	C₂₁H₂₀O₆	368.38		458–37-7	APP/V717 double transgenic mice	Reduced the positive expression of Aβ and P-tau protein in the brain tissues.	[102]
Curcumin-macrophage exosome	–	–	–	–	–	OA-induced Tau hyperphosphorylation	Reduced Tau hyperphosphorylation by inhibiting the AKT/GSK-3β signaling pathway.	[103]
Angelica sinensis	Angelica sinensis (Oliv.) Diels	–	–	–	–	Bilateral common carotid artery ligation model (2VO)	Reduced the expression of phosphorylated Tau (T231, S396); inhibited the Akt/GSK3β pathway and promoting the expression of BACE-1 and BDNF.	[106]
Ligustrazine	Ligusticum chuanxiong Hort.	C₈H₁₂N₂	136.19		1124–11-4	Bilateral hippocampal injections of Aβ25-35 induced in SD rats	Downregulated GSK-3β positive expression and inhibited β-catenin degradation; Activate Wnt signaling pathway.	[113]
Cornus officinalis polysaccharide	Cornus officinalis Sieb. et Zucc.	–	–	–	–	D-galactose combined with Aβ1~40 to prepare AD model	Inhibited of GSK-3β expression in the hippocampal CA1 region of AD rats; reduced the positive expression of p-tau(Ser422) phosphorylation sites.	[114,115]
Schisandra chinensis acidic polysaccharide (SCP-A)	Schisandra chinensis	–	–	–	–	Bilateral hippocampal injections of Aβ25-35 induced in SD rats	Reduced Tau protein phosphorylation at Tau Ser199, Tau Ser396 and Tau Ser404 loci and GSK-3β (Tyr216) expression levels; and increased GSK-3β (Ser9)expression levels.	[116]
Osthole	Cnidium monnieri(L.)Cuss.	C₁₅H₁₆O₃	244.286		484–12-8	APP/PS1 double transgenic mice;	Reduced p-tau(ser202) protein expression and enhanced PI3K, p-Akt/Akt and p-Gsk3β/Gsk3β protein expression levels.	[117]
Tanshinone IIA	Salvia miltiorrhiza Bunge	C₁₉H₁₈O₃	294.344		100,210–65-9	Aβ25-35-induced primary cultured cortical neurons; Aβ1-42-induced AD rats	Inhibition of cytoplasmic p25 expression and CDK-5 activation; decreased GSK-3β phosphorylation at the Tyr216 site and increased GSK-3β phosphorylation at the Ser9 site	[121,122]
Senegenin	Polygala tenuifolia Willd.	C₃₀H₄₅ClO₆	537.128		2469–34-3	Bilateral hippocampal injections of Aβ25-35 induced in SD rats	Decreased the total tau protein content, tau protein Ser396 phosphorylation level and PKA protein expression level; increased the expression level of PP2A protein.	[96]
Baicalin	Scutellaria baicalensis Georgi	C₂₁H₁₈O₁₁	446.361		21,967–41-9	Tau transgenic mice (TauP310L)	Reduced the expression level of p62 protein and increased the levels of Beclin-1 and LC3B, thereby enhancing the autophagy ability of transgenic mice.	[146]
Celastrol	Tripterygium wilfordii Hook. f.	C₂₉H₃₈O₄	450.61		34,157–83-0	Aβ25-35 induced PC12 cells; rapidly aging SAMP8 mice	Promoted TFEB translocation from the cytoplasm to the nucleus, enhances autophagy and lysosomal biological activity; degradated of phosphorylated Tau aggregates.	[153]