A review on chemistry, source and therapeutic potential of lambertianic acid

Abstract Lambertianic acid (LA) is a diterpene bioactive compound mainly purified from different species of Pinus. It is an optical isomer of another natural compound daniellic acid and was firstly purified from Pinus lambertiana. LA can be synthesized in laboratory from podocarpic acid. It has been reported to have potential health benefits in attenuating obesity, allergies and different cancers including breast, liver, lung and prostate cancer. It exhibits anticancer properties through inhibiting cancer cell proliferation and survival, and inducing apoptosis, targeting major signalling components including AKT, AMPK, NFkB, COX-2, STAT3, etc. Most of the studies with LA were done using in vitro models, thus warranting future investigations with animal models to evaluate its pharmacological effects such as antidiabetic, anti-inflammatory and neuroprotective effects as well as to explore the underlying molecular mechanisms and toxicological profile. This review describes the chemistry, source, purification and therapeutic potentials of LA and it can therefore be a suitable guideline for any future study with LA.

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Cordycepin Exerts Neuroprotective Effects via an Anti-Apoptotic Mechanism based on the Mitochondrial Pathway in a Rotenone-Induced Parkinsonism Rat Model

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190905152138 ◽

2019 ◽

Vol 18 (8) ◽

pp. 609-620 ◽

Cited By ~ 5

Author(s):

Xin Jiang ◽

Pei-Chen Tang ◽

Qin Chen ◽

Xin Zhang ◽

Yi-Yun Fan ◽

...

Keyword(s):

Rat Model ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Therapeutic Potential ◽

Neuroprotective Effect ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Neuroprotective Effects ◽

Cyt C

Background: Cordycepin (Cor), one of the major bioactive components of the traditional Chinese medicine Cordyceps militaris, has been used in clinical practice for several years. However, its neuroprotective effect remains unknown. Aim: The purpose of the study was to evaluate the neuroprotective effects of Cor using a rotenoneinduced Parkinson’s Disease (PD) rat model and to delineate the possible associated molecular mechanisms. Methods: In vivo, behavioural tests were performed based on the 10-point scale and grid tests. Levels of dopamine and its metabolites in the striatum and the numbers of TH-positive neurons in the Substantia Nigra pars compacta (SNpc) were investigated by high-performance liquid chromatography with electrochemical detection and immunohistochemical staining, respectively. In vitro, cell apoptosis rates and Mitochondrial Membrane Potential (MMP) were analysed by flow cytometry and the mRNA and protein levels of Bax, Bcl-2, Bcl-xL, Cytochrome c (Cyt-c), and caspase-3 were determined by quantitative real-time PCR and western blotting. Results: Showed that Cor significantly improved dyskinesia, increased the numbers of TH-positive neurons in the SNpc, and maintained levels of dopamine and its metabolites in the striatum in rotenone- induced PD rats. We also found that apoptosis was suppressed and the loss of MMP was reversed with Cor treatment. Furthermore, Cor markedly down-regulated the expression of Bax, upregulated Bcl-2 and Bcl-xL, inhibited the activation of caspase-3, and decreased the release of Cyt-c from the mitochondria to the cytoplasm, as compared to those in the rotenone-treated group. Conclusion: Therefore, Cor protected dopamine neurons against rotenone-induced apoptosis by improving mitochondrial dysfunction in a PD model, demonstrating its therapeutic potential for this disease.

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Resveratrol as a Therapeutic Agent for Alzheimer’s Disease

BioMed Research International ◽

10.1155/2014/350516 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 50

Author(s):

Teng Ma ◽

Meng-Shan Tan ◽

Jin-Tai Yu ◽

Lan Tan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanisms ◽

Therapeutic Agent ◽

Red Wine ◽

Therapeutic Potential ◽

Neuroprotective Effect ◽

Neuroprotective Effects

Alzheimer’s disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβaccumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.

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Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential

Current Pharmaceutical Design ◽

10.2174/1381612826666201112144006 ◽

2020 ◽

Vol 26 ◽

Author(s):

Nimra Javaid ◽

Muhammad Ajmal Shah ◽

Azhar Rasul ◽

Zunera Chauhdary ◽

Uzma Saleem ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Ellagic Acid ◽

Molecular Mechanisms ◽

Neurodegenerative Disorder ◽

Therapeutic Potential ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Acetylcholinesterase Activity ◽

Neuroprotective Effects

: Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

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Synergistic Action of Flavonoids, Baicalein, and Daidzein in Estrogenic and Neuroprotective Effects: A Development of Potential Health Products and Therapeutic Drugs against Alzheimer’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/635694 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 21

Author(s):

Roy C. Y. Choi ◽

Judy T. T. Zhu ◽

Amanda W. Y. Yung ◽

Pinky S. C. Lee ◽

Sherry L. Xu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transcriptional Activation ◽

Estrogenic Activity ◽

Neuroprotective Effects ◽

Potential Health ◽

Amyloid A ◽

Therapeutic Drugs ◽

Health Products

Despite the classical hormonal effect, estrogen has been reported to mediate neuroprotection in the brain, which leads to the searching of estrogen-like substances for treating neurodegenerative diseases. Flavonoids, a group of natural compounds, are well known to possess estrogenic effects and used to substitute estrogen, that is, phytoestrogen. Flavonoid serves as one of the potential targets for the development of natural supplements and therapeutic drugs against different diseases. The neuroprotection activity of flavonoids was chosen for a possible development of anti-Alzheimer's drugs or food supplements. The estrogenic activity of two flavonoids, baicalein and daidzein, were demonstrated by their strong abilities in stimulating estrogen receptor phosphorylation and transcriptional activation of estrogen responsive element in MCF-7 breast cells. The neuroprotection effects of flavonoids againstβ-amyloid (Aβ) were revealed by their inhibition effects onin vitroAβaggregation and Aβ-induced cytotoxicity in PC12 neuronal cells. More importantly, the estrogenic and neuroprotective activities of individual flavonoid could be further enhanced by the cotreatment in the cultures. Taken together, this synergistic effect of baicalein and daidzein might serve as a method to improve the therapeutic efficacy of different flavonoids against Aβ, which might be crucial in developing those flavonoidsin treating Alzheimer's disease in the future.

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Alantolactone: A Natural Plant Extract as a Potential Therapeutic Agent for Cancer

Frontiers in Pharmacology ◽

10.3389/fphar.2021.781033 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuan Cai ◽

Kewa Gao ◽

Bi Peng ◽

Zhijie Xu ◽

Jinwu Peng ◽

...

Keyword(s):

Molecular Mechanisms ◽

Cancer Colorectal ◽

Therapeutic Potential ◽

Inhibitory Effects ◽

Cytotoxic Effects ◽

Cancer Breast ◽

Anticancer Effects ◽

Inula Helenium

Alantolactone (ALT) is a natural compound extracted from Chinese traditional medicine Inula helenium L. with therapeutic potential in the treatment of various diseases. Recently, in vitro and in vivo studies have indicated cytotoxic effects of ALT on various cancers, including liver cancer, colorectal cancer, breast cancer, etc. The inhibitory effects of ALT depend on several cancer-associated signaling pathways and abnormal regulatory factors in cancer cells. Moreover, emerging studies have reported several promising strategies to enhance the oral bioavailability of ALT, such as combining ALT with other herbs and using ALT-entrapped nanostructured carriers. In this review, studies on the anti-tumor roles of ALT are mainly summarized, and the underlying molecular mechanisms of ALT exerting anticancer effects on cells investigated in animal-based studies are also discussed.

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Delphinidin and Its Glycosides’ War on Cancer: Preclinical Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms222111500 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11500

Author(s):

Anshul Sharma ◽

Hyo-Kyoung Choi ◽

Yeon-Kye Kim ◽

Hae-Jeung Lee

Keyword(s):

Molecular Mechanisms ◽

Future Research ◽

Natural Health Products ◽

Cell Protection ◽

Anticancer Properties ◽

Dietary Antioxidant ◽

Health Products ◽

Antioxidant Supplements

Until now, several studies have looked at the issue of anthocyanin and cancer, namely the preventive and inhibitory effects of anthocyanins, as well as the underlying molecular processes. However, no targeted review is available regarding the anticarcinogenic effects of delphinidin and its glycosides on various cancers and their plausible molecular mechanisms. Considerable evidence shows significant anticancer properties of delphinidin-rich preparations and delphinidin alone both in vitro and in vivo. This review covers the in vitro and preclinical implications of delphinidin-mediated cell protection and cancer prevention; thus, we strongly recommend that delphinidin-rich preparations be further investigated as potential functional food, dietary antioxidant supplements, and natural health products targeting specific chronic diseases, including cancer. In addition to in vitro investigations, future research should focus on more animal and human studies to determine the true potential of delphinidin.

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PhyllanthusSuppresses Prostate Cancer Cell, PC-3, Proliferation and Induces Apoptosis through Multiple Signalling Pathways (MAPKs, PI3K/Akt, NFκB, and Hypoxia)

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/609581 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 12

Author(s):

Yin-Quan Tang ◽

InduBala Jaganath ◽

Rishya Manikam ◽

Shamala Devi Sekaran

Keyword(s):

Molecular Mechanisms ◽

Prostate Cancer Cell ◽

Prostate Adenocarcinoma ◽

Signalling Pathways ◽

Differentially Expressed Proteins ◽

Signalling Molecules ◽

Anticancer Properties ◽

Anticancer Effects ◽

2D Gel

Phyllanthusis a traditional medicinal plant that has been found to have antihepatitis, antibacterial, and anticancer properties. The present studies were to investigate thein vitromolecular mechanisms of anticancer effects ofPhyllanthus(P. amarus, P. niruri, P. urinaria,andP. watsonii) plant extracts in human prostate adenocarcinoma. The cancer ten-pathway reporter array was performed and revealed that the expression of six pathway reporters were significantly decreased (Wnt, NFκB, Myc/Max, hypoxia, MAPK/ERK, and MAPK/JNK) in PC-3 cells after treatment withPhyllanthusextracts. Western blot was conducted and identified several signalling molecules that were affected in the signalling pathways including pan-Ras, c-Raf, RSK, Elk1, c-Jun, JNK1/2, p38 MAPK, c-myc, DSH,β-catenin, Akt, HIF-1α, GSK3β, NFκB p50 and p52, Bcl-2, Bax, and VEGF, in treated PC-3 cells. A proteomics-based approach, 2D gel electrophoresis, was performed, and mass spectrometry (MS/MS) results revealed that there were 72 differentially expressed proteins identified in treated PC-3 cells and were involved in tumour cell adhesion, apoptosis, glycogenesis and glycolysis, metastasis, angiogenesis, and protein synthesis and energy metabolism. Overall, these findings suggest thatPhyllanthuscan interfere with multiple signalling cascades involved in tumorigenesis and be used as a potential therapeutic candidate for treatment of cancer.

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Potential Health Benefits Of A Pomegranate Extract, Rich In Phenolic Compounds, In Intestinal Inflammation

Current Nutrition & Food Science ◽

10.2174/1573401317666210222103032 ◽

2021 ◽

Vol 17 ◽

Author(s):

Marco Raffaele ◽

Khaled Greish ◽

Luca Vanella ◽

Giuseppe Carota ◽

Fatemah Bahman ◽

...

Keyword(s):

Bioactive Compounds ◽

Molecular Mechanisms ◽

Intestinal Inflammation ◽

Inflammatory Marker ◽

Experimental Models ◽

Cellular Damage ◽

Experimental Conditions ◽

Potential Health

Background: Pomegranate is a fruit rich in bioactive compounds such as punicalagins, gallic acid, and ellagic acid derivatives. It has been widely used since ancient times in traditional medicine for a wide variety of diseases. It has been reported that bioactive compounds, such as polyphenols, are able to induce the expression of cytoprotective enzymes, including HO-1. The contribution of HO-1 activity to the prevention of intestinal inﬂammation has been shown in different models of Inﬂammatory bowel diseases (IBD). Objective: Aim of the present research was to investigate the molecular mechanisms involved in the beneficial effects of a pomegranate extract (PE), rich in bioactive compounds in intestinal inflammation. Methods: Caco-2 cells exposed to LPS and DSS induced colitis were chosen as convenient experimental models of intestinal inflammation. Results: Results obtained in our experimental conditions, showed that PE in vitro was able to induce HO-1 and to reduce cellular damage and oxidative stress through increase of GSH levels. Moreover, PE was able to decrease the pro-inflammatory marker IL-8 levels and to activate TIGAR pathway. The results obtained in vivo, in agreement with the data obtained in vitro, highlighted the ability of PE to reduce intestinal inflammation, preserve the colon length and histological features and reduce IL-6 levels compared to the DSS treated group. Conclusion: PE, rich in bioactive compounds, could contribute, as supportive therapy, to enhance the effects of the conventional therapeutic strategies to the management of IBD.

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Pharmacological Inhibition of Caspase-8 Suppresses Inflammation-Induced Angiogenesis in the Cornea

Biomolecules ◽

10.3390/biom10020210 ◽

2020 ◽

Vol 10 (2) ◽

pp. 210

Author(s):

Yunzhe Tian ◽

He Li ◽

Xiuxing Liu ◽

Lihui Xie ◽

Zhaohao Huang ◽

...

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Corneal Neovascularization ◽

Caspase 8 ◽

Inhibitory Effects ◽

Toll Like Receptor 4 ◽

Pharmacological Inhibition ◽

Cytokines And Chemokines ◽

Tnf Α

Inflammation-induced angiogenesis is closely related to many diseases and has been regarded as a therapeutic target. Caspase-8 has attracted increasing attention for its immune properties and therapeutic potential in inflammatory disorders. The aim of our study is to investigate the clinical application of pharmacological inhibition of caspase-8 and the underlying molecular mechanisms in inflammation-induced angiogenesis in the cornea. A model of alkali burn (AB)-induced corneal neovascularization (CNV) in C57BL/6 wild-type (WT) mice and toll-like receptor 4 knockout (Tlr4-/-) mice was used. We found that AB increased caspase-8 activity and the pharmacological inhibition of caspase-8 exerted substantial inhibitory effects on CNV, with consistent decreases in caspase-8 activity, inflammatory cell infiltration, macrophage recruitment and activation, VEGF-A, TNF-α, IL-1β, MIP-1, and MCP-1 expression in the cornea. In vitro, caspase-8 mediated TLR4–dependent chemokines and VEGF-A production by macrophages. The TLR4 knockout significantly alleviated CNV, suppressed caspase-8 activity and downregulated expression of inflammatory cytokines and chemokines after AB. Taken together, these findings provide the first demonstration that the pharmacological inhibition of caspase-8 suppresses inflammation-induced angiogenesis and support the use of a pharmacological caspase-8 inhibitor as a novel clinical treatment for CNV and other angiogenic disorders.

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Natural compounds attenuate heavy metal-induced PC12 cell damage

Journal of International Medical Research ◽

10.1177/0300060520930847 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052093084

Author(s):

Lina Yang ◽

Keshu Shen ◽

Dongping Ji

Keyword(s):

Heavy Metal ◽

Pc12 Cells ◽

Pc12 Cell ◽

Therapeutic Potential ◽

Cell Damage ◽

Mitochondrial Protein ◽

Natural Compounds ◽

Alpha Tocopherol ◽

Neuroprotective Effects

Objectives To investigate the neuroprotective effects of six natural compounds (caffeine, gallic acid, resveratrol, epigallocatechin gallate [EGCG], L-ascorbic acid and alpha tocopherol [Vitamin E] on heavy metal-induced cell damage in rat PC12 cells. Methods In this in vitro experiment, rat PC12 cells were exposed to four heavy metals (CdCl2, HgCl2, CoCl2 and PbCl2) at different concentrations and cell apoptosis, necrosis and oxidative stress were assessed with and without the addition of the six natural compounds. Results The metals decreased cell viability but the natural compounds attenuated their effects on apoptosis, necrosis and reactive oxygen species (ROS) levels. Mitochondrial protein changes were involved in the regulation. Conclusion Overall, the natural compounds did provide protection against the metal-induced PC12 cell damage. These data suggest that natural compounds may have therapeutic potential against metal-induced neurodegenerative disease.

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