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Anti-Neuroinflammatory and Neuroprotective Effects of Caffeic Acid in Experimental Models of Neurodegeneration: A
Radhika Bhat1, Alosh Greeny1, Gollapalle Lakshminarayanashastry Viswanatha1,2
1Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Abstract:
Caffeic acid, a naturally occurring polyphenol found in various dietary sources, has gained considerable interest for its antioxidant, anti-inflammatory, and neuroprotective properties. Preclinical studies suggest that caffeic acid may exert beneficial effects in models of Alzheimer's disease, Parkinson's disease, cerebral ischaemia, ageing, diabetes-associated cognitive decline, and neuroinflammation. To assess the neuroprotective activity of caffeic acid in neurodegenerative diseases. After performing a detailed literature search across various databases, such as Google Scholar, Embase, PubMed, Scopus, and Cochrane, a total of 44 unique studies were identified based on the framed eligibility criteria. This meta-analysis demonstrated that caffeic acid exerts significant effect on neurobiomarker panel: amyloid-β accumulation (IV: -1.84 [-3.08, -0.61], 95% CI, p = 0.004, I2 = 8%), GFAP (IV: -2.03 [-2.91, -1.15], 95% CI, p < 0.00001,), AchE (IV: -1.98 [-3.44, -0.52], 95% CI, p = 0.008, I2 = 85%), BDNF (IV: 1.14 [0.20, 2.09], 95% CI, p = 0.02, I2 = 57%); Oxidative stress markers such as MDA (IV: -4.60 [-6.66, -2.55], 95%CI, p < 0.0001, I2 = 99%) and LPO (IV: -2.12 [-3.49, -0.75], 95% CI, p = 0.002, I2 = 98%), SOD (IV: 4.90 [3.72, 6.08], 95% CI, p < 0.00001, I2 = 99%), CAT (IV: 21.35 [12.10, 30.61], 95% CI, p < 0.00001, I2 = 94%), GSH (IV: 6.86 [5.28, 8.44], 95% CI, p < 0.00001, I2 = 99%); Neuroinflammatory parameters including TNF-α (IV: -4.23 [-5.89, -2.57], 95% CI, p < 0.00001, I2 = 83%), IL-6 (IV: -3.07 [-4.69, -1.45], 95% CI, p = 0.0002, I2 = 78%) and IL-1β (IV: -5.09 [-8.12, -2.07], 95% CI, p = 0.0010, I2 = 61%); Behavioural parameters like forced swim test (IV: -2.22 [-3.83, -0.61], 95% CI, p = 0.007, I2 = 86%), open field test- number of rearing's (IV: 12.50 [0.55, 24.45], 95% CI, p = 0.04, I2 = 89%), elevated plus maze test- time spent in open arms (IV: -30.45 [-53.67, -7.22], 95% CI, p = 0.01, I2 = 81%); Apoptosis (Caspase-3) parameters (IV: -28.46 [-52.22, -4.70], 95% CI, p = 0.02, I2 = 95%). Caffeic acid showed significant neuroprotective activity in neurodegenerative diseases based on pre-clinical evidence, making it a promising molecule for future RCTs.
