Multitarget Activities of Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Against Alzheimer's Disease.

Chantha Chheng,Pornthip Waiwut,Supaporn Pitiporn,Orawan Monthakantirat,Natdanai Musigavong,Supawadee Daodee,Kusawadee Plekratoke,Chantana Boonyarat,Yaowared Chulikhit,Pakakrong Kwankhao

doi:10.3390/ph13050079

Abstract

The Kleeb Bua Daeng formula (KBD) is a Thai traditional medicine for brain health promotion. On the basis of the activities of its individual components, the KBD could have good potential for the treatment of Alzheimer’s disease (AD). Herein, we investigated the KBD as an AD treatment. The ethanol extracts of KBD and its components, i.e., Nelumbo nucifera (NN), Piper nigrum fruits (BP), and the aerial part of Centella asiatica (CA) exhibited antioxidant activity, as determined by both ABTS and DPPH assays. The Ellman’s assay revealed that the KBD, NN, and BP showed an ability to inhibit acetylcholinesterase. The thioflavin T assay indicated that the KBD, NN, BP, and CA inhibited beta-amyloid aggregation. The neuroprotection and Western blot analysis revealed that the KBD reduced H2O2-induced neuronal cell death by inhibiting the expression of pro-apoptotic factors, i.e., cleaved caspase-9 and -3, p-P65, p-JNK, and p-GSK-3β, as well as by inducing expression of anti-apoptotic factors, i.e., MCl1, BClxl, and survivin. Furthermore, the KBD could improve scopolamine induced memory deficit in mice. Our results illustrate that the KBD with multimode action has the potential to be employed in AD treatment. Thus, the KBD could be used as an alternative novel choice for the prevention and treatment of patients with AD.

Highlights

Alzheimer’s disease (AD) is a multifactorial neurological disorder categorized by memory impairment, progressive decline in cognitive functions, and changes in behaviors and moods [1]
There has been no previous study investigating the Kleeb Bua Daeng formula (KBD) as a therapeutic for AD. This current study has investigated the effects of the KBD and its components on the following four targets in the pathological cascade of AD: (i) antioxidant activity, (ii) cholinesterase function, (iii) beta amyloid aggregation, and (iv) neuroprotection in vitro
T3o1.c1o7m± p1.a4r8eathe activities amonNg etlhuemcboomnupcoifnerean(tNs,Nth) e KBD extract a4t33.8m5 ±g/0m.4L6 abnd its components at e3q3u.8iv3a±le2n.2t2aamounts (NN, BacPt,ivaintydCP,eCnifpoAtpellelloaratwna1isegimadrutigmbca/ym((BCBLPPA)) )wanedreCaAssa(Fyiegdu.rTeh112e2)9..N.69O48Nu±±re00xr..2et6r5s3audcclttsposhssoewsseeddtthhaet mthoesrtapd41o29itc..e12an21lt±±srca50ad..v55i4e9cnabcgl isncgavaecntigviintgy of the KBD is mainly provided by Nelumbo nucifera (NN)

Summary

Introduction

Alzheimer’s disease (AD) is a multifactorial neurological disorder categorized by memory impairment, progressive decline in cognitive functions, and changes in behaviors and moods [1]. The incidence rate of AD has presented an exponential increase, in people over 65 years of age; the disease currently affects over 33 million people worldwide [2,3,4]. The current therapeutic approaches for AD include the following: (a) acetylcholinesterase (AChE) inhibitors such as donepezil, rivastigmine, and galantamine and (b) the NMDA receptor antagonist, memantine [13]. While these drugs can be used for reducing symptoms, they are not effective for curing AD.

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