Challenges associated with curcumin therapy in Alzheimer disease

Author(s):  
Abdenour Belkacemi ◽  
Sihem Doggui ◽  
Lé Dao ◽  
Charles Ramassamy

Curcumin, the phytochemical agent in the spice turmeric, which gives Indian curry its yellow colour, is also a traditional Indian medicine. It has been used for millennia as a wound-healing agent and for treating a variety of ailments. The antioxidant, anti-inflammatory, antiproliferative and other properties of curcumin have only recently gained the attention of modern pharmacology. The mechanism of action of curcumin is complex and multifaceted. In part, curcumin acts by activating various cytoprotective proteins that are components of the phase II response. Over the past decade, research with curcumin has increased significantly. In vitro and in vivo studies have demonstrated that curcumin could target pathways involved in the pathophysiology of Alzheimer disease (AD), such as the β-amyloid cascade, tau phosphorylation, neuroinflammation or oxidative stress. These findings suggest that curcumin might be a promising compound for the development of AD therapy. However, its insolubility in water and poor bioavailability have limited clinical trials and its therapeutic applications. To be effective as a drug therapy, curcumin must be combined with other drugs, or new delivery strategies need to be developed.

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5391
Author(s):  
Zheng Liu ◽  
Ming Bian ◽  
Qian-Qian Ma ◽  
Zhuo Zhang ◽  
Huan-Huan Du ◽  
...  

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.


2013 ◽  
Vol 4 (6) ◽  
pp. 973-982 ◽  
Author(s):  
Alaa H. Abuznait ◽  
Hisham Qosa ◽  
Belnaser A. Busnena ◽  
Khalid A. El Sayed ◽  
Amal Kaddoumi

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Brajendra Tiwari ◽  
Richa Pahuja ◽  
Pradeep Kumar ◽  
Srikanta Kumar Rath ◽  
Kailash Chand Gupta ◽  
...  

ABSTRACT Leishmaniasis chemotherapy remains very challenging due to high cost of the drug and its associated toxicity and drug resistance, which develops over a period of time. Combination therapies (CT) are now in use to treat many diseases, such as cancer and malaria, since it is more effective and affordable than monotherapy. CT are believed to represent a new explorable strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite Leishmania. In the present study, we investigated the effect of a combination of a traditional Indian medicine (ayurveda), a natural product curcumin and miltefosine, the only oral drug for visceral leishmaniasis (VL) using a Leishmania donovani-hamster model. We developed an oral nanoparticle-based formulation of curcumin. Nanoformulation of curcumin alone exhibited significant leishmanicidal activity both in vitro and in vivo. In combination with miltefosine, it exhibited a synergistic effect on both promastigotes and amastigotes under in vitro conditions. The combination of these two agents also demonstrated increased in vivo leishmanicidal activity accompanied by increased production of toxic reactive oxygen/nitrogen metabolites and enhanced phagocytic activity. The combination also exhibited increased lymphocyte proliferation. The present study thus establishes the possible use of nanocurcumin as an adjunct to antileishmanial chemotherapy.


2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Zhijun Wang ◽  
Jeffrey Wang ◽  
Patrick Chan

Type II diabetes mellitus (T2DM) is a fast-growing epidemic affecting people globally. Furthermore, multiple complications and comorbidities are associated with T2DM. Lifestyle modifications along with pharmacotherapy and patient education are the mainstay of therapy for patients afflicted with T2DM. Western medications are frequently associated with severe adverse drug reactions and high costs of treatment. Herbal medications have long been used in the treatment and prevention of T2DM in both traditional Chinese medicine (TCM) and traditional Indian medicine (TIM). This review examinesin vivo,in vitro, and clinical evidence supporting the use of various herbs used in TCM and TIM. The problems, challenges, and opportunities for the incorporation of herbal frequently used in TCM and TIM into Western therapy are presented and discussed.


2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Tarin M. Bigley ◽  
Monica Xiong ◽  
Muhammad Ali ◽  
Yun Chen ◽  
Chao Wang ◽  
...  

Abstract Background The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition. Methods We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD. Results We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, −omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD. Conclusion Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.


2021 ◽  
Vol 11 (10) ◽  
pp. 228-238
Author(s):  
Ankita Dutta ◽  
R. K. Patil ◽  
H. C. l Pati

Curcumin is used as traditional Indian and Chinese medicine in order to treat various diseases as well as used as a wound healing agent. Two to five percent in turmeric is curcumin; turmeric is available in yellow colour mainly obtained from polyphenolic pigment and fat-soluble substance called as curcuminoids, mostly used in the Indian subcontinent. Various clinical trials are conducted for understanding the wide range of therapeutic uses of curcumin. According to the studies, it shows that curcumin manifests very poor oral bioavailability, and forms numerous curcumin metabolites are formed after metabolism, although the bioavailability is low but the therapeutic activity of the curcumin for the various diseases, and for treatment of the disease enhancement of bioavailability of the curcumin in the future is necessary. According to the recent study on nanocurcumin with the size less than 100 nm which is an application of polymer-based nanoparticle of curcumin. It was observed that this polymer-based nanoparticle of curcumin has similar in vitro activity as that of free curcumin in pancreatic cell lines. In in-vivo study performed with the healthy volunteers a cream containing curcuminoid loaded SLNs was topically applied over the cream containing free curcuminoid showed the improvement in efficacy. Therefore, various techniques are developing for the nanoparticulate formulations. Key words: Curcuminoids, bioavailability, nanoparticulate, nanocurcumin, polyphenolic.


2001 ◽  
Vol 5 (8) ◽  
pp. 645-651
Author(s):  
M. Peeva ◽  
M. Shopova ◽  
U. Michelsen ◽  
D. Wöhrle ◽  
G. Petrov ◽  
...  
Keyword(s):  

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