Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia

Abstract

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.

Neuroprotective Effect of Marrubium vulgare Extract in Scopolamine-Induced Cognitive Impairment in Rats: Behavioral and Biochemical Approaches

“…Analysis revealed that, as expected, Sco suppressed hippocampal and cortical pCREB/BDNF protein expression, leading to memory impairment in rats. This aligns with literature data and findings from our previous research [ 22 , 25 , 97 ]. Treatment with M. vulgare significantly increased pCREB expression in the cortex of the animals with dementia.…”

“…It is noteworthy that the LC is activated in response to novelty [ 87 ] and arousal [ 88 ], and its degeneration is a hallmark of AD [ 89 ]. Sco treatment has been shown to depress the monoaminergic systems in the cortex and hippocampus, a finding corroborated by our previous research [ 22 , 25 , 64 ]. Treatment with M. vulgare has been observed to positively affect the NA system but did not significantly impact the Sero system.…”

“…The administration of Sco altered the behavior and biochemical profiles of the experimental animals. Deficiency in spatial memory, associative memory, and recognition memory performance are reported in our studies and by other researchers [ 20 , 21 , 22 , 23 , 24 , 25 , 64 ]. In addition to disrupting the brain cholinergic system (evidenced by increased AChE activity and reduced ACh levels), Sco treatment also escalated oxidative stress, diminished brain monoamine levels (DA, NA, and Sero), and attenuated BDNF/CREB signaling in the brain [ 22 , 23 , 24 , 25 , 63 , 74 , 75 , 76 ].…”

“…This approach represents the most commonly used model of pharmacologically induced dementia [ 19 , 20 ]. Sco administration leads to changes in exploratory behavior, as well as spatial, associative, and recognition memory in experimental animals [ 20 , 21 , 22 , 23 , 24 , 25 ]. In addition, impairment in antioxidant defense systems, increased oxidative stress, mitochondrial dysfunction, apoptosis, and neuroinflammation have also been reported [ 26 ].…”

“…Our previous research with Sideritis scardica and Clinopodium vulgare , also members of the Lamiaceae family, showed an ameliorative memory effect in experimental models of dementia in rodents. They positively impact spatial working and recognition memory, affected by scopolamine [ 22 ]. Notably, the combination of S. scardica and C. vulgare demonstrated the best recognition memory-preserving effect, strong antioxidant activity, and a notable monoaminergic preservation effect in the cortex.…”