Targeting cognitive deficits - Gardenia jasminoides and other natural products The beneficial effects of Gardenia jasminoides in cognitive disorders has been linked to various mechanisms such as anti-inflammatory activity, anti-oxidant activity, promotion of neurite outgrowth, reductions in endoplasmic reticulum stress and activation of Glucagon- like Peptide 1 Receptor [1]. In general, cognitive disorders such as the deficits from major depressive illness can be treatment resistant and some have considered the use of natural products to improve recovery of these deficits [2]. Some examples are B. monnieri, H. citrina, Rhodiola rosea L., Theobroma cacao L., and V. vinifera. Phytochemicals exert neuroprotective effects due, in part, to their anti-inflammatory and antioxidant properties, with evidence strongly suggesting that they can decrease the cognitive symptom of depression. The improvements in cognition have been linked to BDNF-TrkB sigmalling and reductions in oxidative stress and neuroinflammation Geniposide offers: - Neuronal protection - increase autophagy and inhibit apoptosis by regulating the function of mTOR - improving metabolic abnormalities, regulating oxidative stress, inhibiting neuronal apoptosis, and reducing inflammation. - enhancing cholinergic neurotransmission - modulating NMDAR subunitys - regulate the activity of the mechanistic target of rapamycin (mTOR) by activating glucagon- like peptide-1 (GLP-1) receptors. - improving oxidative stress and mitochondrial dysfunction - modulating PI3K/Akt/GSK-3β signalling pathway - downregulate the expression level of proinflammatory cytokines - upregulate the mRNA expression of BDNF and TrkB 1 From Li et al. (2020) [2] Increasing evidence also suggests that geniposide (A) and genipin (B) can improve the symptoms related to the progression of neurodegenerative conditions with significant increases in learning ability, memory-related functions, and enhancement of cognitive function Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease http://dx.doi.org/10.1016/B978-0-12-411462-3.00024-2 Potential effect of herbal antidepressants on cognitive deficit: Pharmacological activity and possible molecular mechanism 2 https://doi.org/10.1016/j.jep.2020.112830 Zhang W, Zhang F, Hu Q, Xiao X, Ou L, Chen Y, Luo S, Cheng Y, Jiang Y, Ma X, Zhao Y. The emerging possibility of the use of geniposide in the treatment of cerebral diseases: a review. Chin Med. 2021 Aug 28;16(1):86. https://doi.org/10.1186/s13020-021-00486-3 3