Title: Flavanone glycosides inhibit beta-site amyloid precursor protein cleaving enzyme 1 and cholinesterase and reduce Abeta aggregation in the amyloidogenic pathway Ali MY, Jannat S, Edraki N, Das S, Chang WK, Kim HC, Park SK, Chang MS Ref: Chemico-Biological Interactions, 309:108707, 2019 : PubMed
Alzheimer's disease (AD) is a slow but progressive neurodegenerative disease. One of the pathological hallmarks of AD is the progressive accumulation of beta-amyloid (Abeta) in the form of senile plaques, and Abeta insult to neuronal cells has been identified as one of the major causes of AD onset. In the present study, we investigated the anti-AD potential of four flavonoids, naringenin, didymin, prunin, and poncirin, by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). All four flavonoids displayed promising inhibitory activity against AChE, BChE, and BACE1. Structure-activity relationships suggested that glycosylation of naringenin at sugar moieties, and at different positions of the glycosidic linkage, might be closely associated with anti-AD potential. Kinetic and docking studies showed the lowest binding energy and highest affinity for the mixed, competitive, and non-competitive type inhibitors didymin, prunin, and poncirin. Hydrophobic interactions and the number of hydrogen bonds determined the strength of the protein-inhibitor interaction. We also examined the neuroprotective mechanisms by which flavonoids act against Abeta25-35-induced toxicity in PC12cells. Exposure of PC12cells to 10muMAbeta25-35 for 24h resulted in a significant decrease in cell viability. In addition, pretreatment of PC12cells with different concentrations of flavonoids for 1h significantly reversed the effects of Abeta. Furthermore, treatment with the most active flavonoid, didymin, significantly reduced BACE1, APPsbeta, and C99 expression levels in a dose-dependent manner, without affecting amyloid precursor protein (APP) levels in the amyloidogenic pathway. Together, our results indicate that flavonoids, and in particular didymin, exhibit inhibitory activity in vitro, and may be useful in the development of therapeutic modalities for the treatment of AD.
Title: Nelumbo nucifera semen extract improves memory in rats with scopolamine-induced amnesia through the induction of choline acetyltransferase expression Oh JH, Choi BJ, Chang MS, Park SK Ref: Neuroscience Letters, 461:41, 2009 : PubMed
Nelumbo nucifera semen (NNS) is a traditional herb with anti-diarrheal, anti-ganacratia, and tranquilizer-like pharmacological activities. In this study, we examined the anti-amnesic effect of NNS on rats with scopolamine-induced amnesia. Passive avoidance tests, acetylcholinesterase (ACHE) activity, and choline acetyltransferase (CHAT) expression were used to evaluate the NNS anti-amnesic effects. The rats were divided into five groups: the normal group, scopolamine-treated group (1mg/kg; control), NNS (1g/kg) and scopolamine (1mg/kg) co-treatment group, and the ARICEPT (1mg/kg) and scopolamine (1mg/kg) co-treatment group (positive control). The rats were administered the compounds orally for 14 days. The latency time of passive avoidance significantly increased by 54% in the NNS-treated group compared to the scopolamine-treated group. The ACHE activity in the NNS-treated group significantly decreased to 7.35% than that of the control group. CHAT-positive neurons increased by 51.02% in the NNS group compared to the control group. These results suggest that NNS extract improves scopolamine-induced dementia by inhibiting ACHE activity and inducing CHAT expression.
Title: Control of Mansonia mosquitos, vectors of brugian filariasis in Sarawak, Malaysia Chang MS, Chan KL, Ho BC Ref: Southeast Asian J Trop Med Public Health, 2:93, 1993 : PubMed
Two field trials in the control of subperiodic brugian filariasis vectors, mainly Mansonia bonneae and Mansonia dives were carried out in Sarawak, East Malaysia. In the first trial, malathion ultra-low volume (ULV) spray was used to control the Mansonia mosquitos in two filariasis endemic villages. Six spray rounds were applied at biweekly intervals at Kampung Rasau and two spray rounds were applied at monthly intervals in Kampung Triboh. ULV malathion spray reduced biting Ma. bonneae population for 3 days after spraying. The biting density decreased to 50% of the pre-treatment level by the 12th - 13th day and reached the pre-treatment level by the 24th - 25th day. Contact bioassay tests on caged Mansonia mosquitos revealed considerable penetration of the malathion aerosol indoors and relatively adequate coverage outdoors. The estimated number of bites per case per day was 1.09 to 4 times less in the sprayed kampung than in an unsprayed control kampung. The parous and daily survival rates of Mansonia mosquitos were not significantly affected by the spraying. In a second trial, chemotherapy with diethylcarbamazine citrate (DEC) was combined with vector control through indoor residual spraying in Kampung Ampungan. The results were compared with the use of only DEC mass treatment in Kampung Sebangkoi and Kampung Sebamban. The combined control measures in Kampung Ampungan reduced the MfD-50 to 44% of the pre-treatment level over a period of 4 years. In the other two kampungs where only mass DEC therapy was applied, the microfilarial rate and MfD-50 declined significantly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. The total insecticidal impact for Ma. bonneae was 3.9 to 1 indoors and 2.7 to 1 outdoors. These results indicated that quarterly pirimiphos-methyl indoor spraying used in integrated control could reduce indoor transmission by 3.9 times. The infective rate from the Ma. bonneae dissected in all three kampungs after the interventions, irrespective of DEC treatment alone or in combination with pirimiphos-methyl residual spraying were reduced by two fold. However the infection rate of brugian filarial larvae in Kampung Ampungan was significantly reduced after the use of DEC and insecticide. Annual Transmission Potential (ATP) showed a high significant reduction in Kampung Ampungan (p > 0.001) compared with Kampungs Sebangkoi and Schambam. In Ampungan, the ATP was reduced by 8.5 times indoors after the MDA and insecticidal application and 3 times outdoors. The reduction rate for Sebangkoi and Sebamban both indoors and outdoors were less than 2 fold.
Title: Efficacy of diethylcarbamazine and pirimiphos-methyl residual spraying in controlling brugian filariasis Chang MS, Ho BC, Chan KL Ref: Trop Med Parasitol, 42:95, 1991 : PubMed
A control programme against subperiodic brugian filariasis was implemented in three villages, (Kg. Ampungan, Kg. Sebangkoi and Kg. Sebamban) in Sarawak, Malaysia. In Kampong Ampungan, the mass administration of diethylcarbamazine (DEC-citrate) combined with residual house spraying of pirimiphos-methyl reduced microfilarial rate to 8% of the pre-treatment level and microfilarial density (MfD50) to 44% of the pre-treatment level over a period of four years. In Kampong Sebangkoi and Kampong Sebamban, where only mass DEC therapy was applied, the microfilarial rate and MfD50 declined distinctly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. In Kg, Ampungan, we observed a significant reduction of infective biting rate (88.3%), infection rate (62.5%) and transmission potential (88.1%) of Mansonia bonneae at the fourth spray round. The corresponding reduction rates in Kg. Sebangkoi and Kg. Sebamban were 35.3%, 26.7%, 42.2% and 24%, 30.8% and 15.4% respectively. The biting density of the vector was reduced by 79.8% indoors and 31.8% outdoors at the sprayed village, while only a slight decrease in densities (17.9% indoors and 12.4% outdoors) was observed at the unsprayed village. Bioassay tests revealed that pirimiphos-methyl had a substantial fumigant effect on the vector. The integrated control measure in controlling subperiodic brugian filariasis is discussed.
