Neuroinflammation is pathological evidence of Alzheimer’s disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42)-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight), orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42) into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR) test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats.

Background Alzheimer’s disease (AD) pathogenesis is associated with amyloid-β (Aβ)-induced neuroinflammation. In AD, the activation of microglia caused by Aβ accumulation is followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), and ultimately leads to cognitive impairments. Clausena harmandiana (CH) is a medicinal plant in the Rutaceae family and has been used in folk medicine to relieve illnesses such as stomachache and headache, and as a health tonic. Interestingly, CH root extract (CHRE) has several anti-inflammatory and other pharmacological activities, but there are no studies in AD-like animal models. Objectives This study aims to evaluate the effects of CHRE on cognitive impairments, increased Aβ1–42 protein levels, and neuroinflammation in Aβ1–42-induced rats. Methods Forty-eight adult male Sprague-Dawley rats (250–300 g) were randomly divided into 6 groups (n = 8) of the sham control, V + Aβ, CB + Aβ CHRE125 + Aβ, CHRE250 + Aβ, and CHRE500 + Aβ. Sodium carboxymethylcellulose, Celebrex (10 mg/kg BW) and CHRE (125, 250, and 500 mg/kg BW) were given orally or without any treatment for 35 days. On day 21, aggregated Aβ1–42 at a concentration of 1 μg/μl were injected into both lateral ventricles (1 μl/side) of all treated rats, while sterilized normal saline were injected to untreated rats. Ten days later, the novel object recognition test was performed to assess their recognition memory. At the end of the test period, an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution were used to euthanize all rats. Then Aβ1–42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) were investigated in the cerebral cortex and hippocampus. Results Pretreatment with CHRE at all doses could attenuate short- and long-term impairments in recognition memory. Additionally, CHRE also inhibited the increase of Aβ1–42 protein levels and the expression of inflammatory markers in both brain regions as well as receiving Celebrex. Conclusions This suggests that preventive treatment of CHRE might be a potential therapy against cognitive impairments via reducing Aβ1–42 protein levels and neuroinflammation caused by Aβ1–42.

Kleeb Bua Daeng (KBD) formula has long been used in Thailand as a traditional herbal medicine for promoting brain health. Our recent reports illustrated that KBD demonstrates multiple modes of action against several targets in the pathological cascade of Alzheimer’s disease (AD). The main purpose of the present study was to determine the protective effect and mechanism of KBD in amyloid beta (Aβ)-induced AD rats and its toxicity profiles. Pretreatment with the KBD formula for 14 days significantly improved the short- and long-term memory performance of Aβ-induced AD rats as assessed by the Morris Water Maze (MWM) and object-recognition tests. KBD treatment increased the activities of the antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase; reduced the malondialdehyde content, and; decreased the acetylcholinesterase activity in the rat brain. An acute toxicity test revealed that the maximum dose of 2000 mg/kg did not cause any mortality or symptoms of toxicity. An oral, subchronic toxicity assessment of KBD at doses of 125, 250, and 500 mg/kg body weight/day for 90 days showed no adverse effects on behavior, mortality, hematology, or serum biochemistry. Our investigations indicate that KBD is a nontoxic traditional medicine with good potential for the prevention and treatment of AD.

Background: Neuroinflammation caused by amyloid‐β (Aβ) is associated with Alzheimer’s disease (AD) pathogenesis. In AD, Aβ accumulation can activate the surrounding microglia which followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), results in cognitive impairments. Clausena harmandiana (CH) is an herb in the Rutaceae family and has been used in folk medicine for the treatment of illness such as stomachache and headache, and as a health tonic. It is interesting that CH root extract (CHRE) exhibits various anti-inflammatory and other pharmacological activities, but there has not been any study in Alzheimer's disease-like animal models.Objectives: This study aimed to investigate the effects of CHRE on Aβ1-42-induced cognitive impairments, increased Aβ1-42 protein levels and neuroinflammation. Methods: Forty-eight adult male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groups (n=8). The rats were given 0.5% sodium carboxymethylcellulose, Celebrex® (10 mg/kg BW) or CHRE (125, 250, and 500 mg/kg BW) and not given any treatment by oral gavage for 35 days. On day 21, all treated rats were injected with aggregated Aβ1-42 at a concentration of 1 µg/µl into both lateral ventricles (1 µl/side), while untreated rats were injected with sterilized normal saline. Ten days later, their recognition memory was assessed using the novel object recognition test. At the end of the experiment, all rats were euthanized by an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution, to observe Aβ1-42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) in the cerebral cortex and hippocampus.Results: The results indicated that pretreatment with CHRE at all doses improved impairment of short- and long-term recognition memory. In addition, CHRE significantly decreased Aβ1-42 protein levels and the expression of inflammatory markers in both brain regions as well as pretreatment with Celebrex®.Conclusions: This suggests that CHRE has a potential therapeutic effect against Aβ1-42-induced cognitive impairments by reducing Aβ1-42 protein levels and neuroinflammation.