6-Hydroxycleroda-3,13-dien-15,16-olide Protects Neuronal Cells from Lipopolysaccharide-Induced Neurotoxicity through the Inhibition of Microglia-Mediated Inflammation

Shih, Yu Tzu; Hsu, Ya Yun; Chang, Fang Rong; Wu, Yang Chang; Lo, Yi-Ching

doi:10.1055/s-0029-1186005

Cited by 18 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, 16-Hydroxycleroda-3,13-dien-15,16-olide (HCD) and its analogs extracted from the bark of P. longifolia have strong anti-inflammatory activity [ 99 ]. The enhanced expression of cyto-protective HO-1 factor and anti-inflammatory enzyme in microglia has been reported [ 100 ]. Hereby, the induction of apoptosis in leukemia K562 cells via a reduction in histone-modifying enzymes, PRC2-mediated gene silencing, the reactivation of downstream tumor suppressor gene expressions [ 101 ], via the PI3K/Akt pathway, and Aurora B resulting in gene silencing and cell cycle disturbance [ 102 ].…”

Section: Underlying Mechanisms Of Natural Compound-induced Autophamentioning

confidence: 99%

Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy

Lin

Tsai

et al. 2017

IJMS

131

View full text Add to dashboard Cite

Accumulated evidence indicates that autophagy is a response of cancer cells to various anti-cancer therapies. Autophagy is designated as programmed cell death type II, and is characterized by the formation of autophagic vacuoles in the cytoplasm. Numerous herbs, including Chinese herbs, have been applied to cancer treatments as complementary and alternative medicines, supplements, or nutraceuticals to dampen the side or adverse effects of chemotherapy drugs. Moreover, the tumor suppressive actions of herbs and natural products induced autophagy that may lead to cell senescence, increase apoptosis-independent cell death or complement apoptotic processes. Hereby, the underlying mechanisms of natural autophagy inducers are cautiously reviewed in this article. Additionally, three natural compounds-curcumin, 16-hydroxycleroda-3,13-dien-15,16-olide, and prodigiosin-are presented as candidates for autophagy inducers that can trigger cell death in a supplement or alternative medicine for cancer therapy. Despite recent advancements in therapeutic drugs or agents of natural products in several cancers, it warrants further investigation in preclinical and clinical studies.

show abstract

Section: Underlying Mechanisms Of Natural Compound-induced Autophamentioning

confidence: 99%

Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy

Lin

Tsai

et al. 2017

IJMS

131

View full text Add to dashboard Cite

show abstract

“…Recently, clerodane diterpenes can induce apoptosis of human leukemia HL-60 cells [ 8 ]. 16-Hydroxycleroda-3,13-dien-15,16-olide (HCD) and its analogs, extracted from the bark of P. longifolia exhibits strong anti-inflammatory activities [ 9 ]; enhanced the expression of cyto-protective HO-1 factor and anti-inflammatory enzyme in microglia [ 10 ]; the induction of apoptosis in leukemia K562 cells via both a reduction in histone modifying enzymes PRC2-mediated gene silencing and the reactivation of downstream tumor suppressor gene expressions [ 11 ] and via PI3K-Akt pathway and Aurora B resulting in gene silencing and cell cycle disturbance [ 12 ]. Our previous studies have demonstrated that HCD could cause apoptosis of two CNS cancer cell lines, N18 and C6, via inhibition of FAK-related signaling pathway and accordingly induced the autophagic cell death through ROS generation and p38/ERK1/2 signaling pathway activation [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

The autophagic inhibition oral squamous cell carcinoma cancer growth of 16-hydroxy-cleroda-3,14-dine-15,16-olide

et al. 2017

View full text Add to dashboard Cite

16-hydroxycleroda-3, 13-dine-15, 16-olide (HCD) isolated from Polyalthia longifolia possesses numerous biological activities. Previous studies have reported that HCD can block phosphorylation activity of cancer cells to inhibit tumor cell growth, but the anti-tumor activity in oral squamous cell carcinoma is unrevealed. This study investigates the inhibiting effect of HCD on human OSCC cell growth; thereby, developing a new oral cancer drug. In in vitro cultured human OSCC cells (OECM1 and SAS) were employed to test the inhibitory growth of HCD via cell cytotoxic effect using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, Western blotting, and further determining of the inhibitory efficacy of tumor growth by a xenograft tumor on BALB/c male nude mice (in vivo test). Under various concentrations of HCD and time course treatments were shown to effectively cause cell death and cell-cycle arrest in OECM1 and SAS cells, which was confirmed via a clinical drug (cisplatin) as a positive control. In addition, HCD induced the autophagic cell death in OECM1 and SAS cells by LC3-mediated LC3-I/LC3-II/p62 pathway at the in vitro level. An in vivo assay indicated that HCD could treat oral cancer by deferring tumor growth. These findings provide a favorable assessment for further elucidating the role of HCD that targets autophagic cell death pathways as a potential agent for cancer therapy.

show abstract

“…Under modern chemical and medical research, various antimicrobial and anti-inflammatory compounds are purified and identified, such as 16α-hydroxy-cleroda-3,13(14)-Z-diene-15,16-olide, (3S,4R)-3,4,5-trihydroxy pentanoic acid-1,4-lactone and 16-Oxo-cleroda-3,13E-dien-15-oic acid [12]. HCD has been demonstrated to alleviate lipopolysaccharide-induced microglia inflammation via reducing iNOS, COX-2, and NF-κB gene expression [13]. In addition, HCD repressed COX-2 protein expression in Caco-2 and further ameliorated inflammation in AOM/DSS-induced mice.…”

Section: Discussionmentioning

confidence: 99%

Clerodane Diterpene Ameliorates Inflammatory Bowel Disease and Potentiates Cell Apoptosis of Colorectal Cancer

et al. 2019

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is general term for ulcerative colitis and Crohn's disease, which is chronic intestinal and colorectal inflammation caused by microbial infiltration or immunocyte attack. IBD is not curable, and is highly susceptible to develop into colorectal cancer. Finding agents to alleviate these symptoms, as well as any progression of IBD, is a critical effort. This study evaluates the anti-inflammation and anti-tumor activity of 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) in in vivo and in vitro assays. The result of an IBD mouse model induced using intraperitoneal chemical azoxymethane (AOM)/dextran sodium sulfate (DSS) injection showed that intraperitoneal HCD adminstration could ameliorate the inflammatory symptoms of IBD mice. In the in vitro assay, cytotoxic characteristics and retained signaling pathways of HCD treatment were analyzed by MTT assay, cell cycle analysis, and Western blotting. From cell viability determination, the IC 50 of HCD in Caco-2 was significantly lower in 2.30 µM at 48 h when compared to 5-fluorouracil (5-FU) (66.79 µM). By cell cycle and Western blotting analysis, the cell death characteristics of HCD treatment in Caco-2 exhibited the involvement of extrinsic and intrinsic pathways in cell death, for which intrinsic apoptosis was predominantly activated via the reduction in growth factor signaling. These potential treatments against colon cancer demonstrate that HCD could provide a promising adjuvant as an alternative medicine in combating colorectal cancer and IBD.

show abstract

6-Hydroxycleroda-3,13-dien-15,16-olide Protects Neuronal Cells from Lipopolysaccharide-Induced Neurotoxicity through the Inhibition of Microglia-Mediated Inflammation

Cited by 18 publications

References 28 publications

Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy

Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy

The autophagic inhibition oral squamous cell carcinoma cancer growth of 16-hydroxy-cleroda-3,14-dine-15,16-olide

Clerodane Diterpene Ameliorates Inflammatory Bowel Disease and Potentiates Cell Apoptosis of Colorectal Cancer

Contact Info

Product

Resources

About