PMID: 

Braz J Med Biol Res. 2019 Feb 14 ;52(2):e7843. Epub 2019 Feb 14. PMID: 30785478

Abstract Title: 

Kaempferol suppresses human gastric cancer SNU-216 cell proliferation, promotes cell autophagy, but has no influence on cell apoptosis.

Abstract: 

Gastric cancer remains a serious threat to human health worldwide. Kaempferol is a plant-derived flavonoid compound with a wide range of pharmacological activities. This study aimed to investigate the effects of kaempferol on gastric cancer SNU-216 cell proliferation, apoptosis, and autophagy, as well as underlying potential mechanisms. Viability, proliferation, and apoptosis of SNU-216 cells after kaempferol treatment were evaluated using cell counting kit-8 assay, 5-btomo-2'-deoxyuridine incorporation assay, and annexin V-FITC/PI staining, respectively. Quantitative reverse transcription PCR was performed to measure the mRNA expressions of cyclin D1 and microRNA-181a (miR-181a) in SNU-216 cells. Cell transfection was used to down-regulate the expression of miR-181a. The protein expression levels of cyclin D1, bcl-2, bax, caspase 3, caspase 9, autophagy-related gene 7, microtubule-associated protein 1 light chain 3-I (LC3-I), LC3-II, Beclin 1, p62, mitogen-activated protein kinase (MAPK), extracellular regulated protein kinases (ERK), and phosphatidylinositol 3 kinase (PI3K) in SNU-216 cells were detected using western blotting. Results showed that kaempferol significantly suppressed SNU-216 cell viability and proliferation but had no influence on cell apoptosis. Further results suggested that kaempferol significantly induced SNU-216 cell autophagy. The expression of miR-181a in SNU-216 cells after kaempferol treatment was enhanced. Kaempferol significantly inactivated MAPK/ERK and PI3K pathways in SNU-216 cells. Suppression of miR-181a significantly reversed the kaempferol-induced MAPK/ERK and PI3K pathways inactivation in SNU-216 cells. This research demonstrated that kaempferol suppressed proliferation and promoted autophagy of human gastric cancer SNU-216 cells by up-regulating miR-181a and inactivating MAPK/ERK and PI3K pathways.

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PMID: 

Inflammation. 2014 Oct ;37(5):1453-8. PMID: 24743918

Abstract Title: 

Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice.

Abstract: 

Kaempferol isolated from the root of Zingiberaceae plants galangal and other Chinese herbal medicines have been reported to have anti-inflammatory properties. However, the anti-inflammatory effects of kaempferol on lipopolysaccharide (LPS)-induced mastitis are unknown and their underlying molecular mechanisms remain to be explored. The aim of this study was to evaluate the effects of kaempferol on LPS-induced mouse mastitis. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Kaempferol was injected 1 h before and 12 h after induction of LPS intraperitoneally. The present results showed that kaempferol markedly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner, which were increased in LPS-induced mouse mastitis. Furthermore, kaempferol suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 subunit and the degradation of its inhibitor IκBα. All results suggest that anti-inflammatory effects of kaempferol against the LPS-induced mastitis possibly through inhibition of the NF-κB signaling pathway. Kaempferol may be a potential therapeutic agent for mastitis.

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PMID: 

Pharmacol Rep. 2017 Oct ;69(5):1113-1119. Epub 2017 May 13. PMID: 29031689

Abstract Title: 

Oral administration of kaempferol inhibits bone loss in rat model of ovariectomy-induced osteopenia.

Abstract: 

BACKGROUND: Postmenopausal osteoporosis and osteoporotic fractures constitute an increasing problem in developing countries. Kaempferol, isolated from seeds of Cuscuta chinensis, is an active flavonoid inhibiting in vitro osteoclast activity. The aim of the presented research was an assessment of kaempferol effect on estrogen-deficiency-induced bone structure disturbances in rats.METHODS: The study was performed on 24 Wistar female rats divided into 3 groups: SHAM – rats undergoing a"sham"surgery, OVX-C – control group of animals that underwent ovariectomy, OVX-K – rats undergoing ovariectomy and receiving kaempferol for 8 weeks (from day 56 to day 112).RESULTS: In the OVX-K group, contrary to the OVX-C one, there was no significant decrease in femoral bone mineral density (BMD). A significant increase in Young's modulus was observed in the OVX-K group compared to the OVX-C (15.33±2.51GPa vs. 11.14±1.93GPa, p

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PMID: 

Mol Med Rep. 2016 Mar ;13(3):2791-800. Epub 2016 Feb 2. PMID: 26847723

Abstract Title: 

Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway.

Abstract: 

Kaempferol is a flavonoid compound that has gained importance due to its antitumor properties; however, the underlying mechanisms remain to be fully understood. The present study aimed to investigate the molecular mechanisms of the antitumor function of kaempferol in HepG2 hepatocellular carcinoma cells. Kaempferol was determined to reduce cell viability, increase lactate dehydrogenase activity and induce apoptosis in a concentration‑ and time‑dependent manner in HepG2 cells. Additionally, kaempferol‑induced apoptosis possibly acts via the endoplasmic reticulum (ER) stress pathway, due to the significant increase in the protein expression levels of glucose‑regulated protein 78, glucose‑regulated protein 94, protein kinase R‑like ER kinase, inositol‑requiring enzyme 1α, partial activating transcription factor 6 cleavage, caspase‑4, C/EBP homologous protein (CHOP) and cleaved caspase‑3. The pro‑apoptotic activity of kaempferol was determined to be due to induction of the ER stress‑CHOP pathway, as: i)ER stress was blocked by 4‑phenyl butyric acid (4‑PBA) pretreatment and knockdown of CHOP with small interfering RNA, which resulted in alleviation of kaempferol‑induced HepG2 cell apoptosis; and ii) transfection with plasmid overexpressing CHOP reversed the protective effect of 4‑PBA in kaempferol‑induced HepG2 cells and increased the apoptotic rate. Thus, kaempferol promoted HepG2 cell apoptosis via induction of the ER stress‑CHOP signaling pathway. These observations indicate that kaempferol may be used as a potential chemopreventive treatment strategy for patients with hepatocellular carcinoma.

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PMID: 

Phytother Res. 2019 Feb ;33(2):263-275. Epub 2018 Nov 7. PMID: 30402931

Abstract Title: 

Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review.

Abstract: 

Kaempferol, a natural flavonoid present in several plants, possesses a wide range of therapeutic properties such as antioxidant, anticancer, and anti-inflammatory. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) and human T-cell leukemia/lymphoma virus-I (HTLV-I) signaling pathways, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2). Accordingly, the aim of the present review is to collect information pertaining to the effective role of kaempferol against various degenerative disorders, summarize the antioxidant, anti-inflammatory, anticancer, antidiabetic, and antiaging effects of kaempferol and to review the progress of recent research and available data on kaempferol as a protective and chemotherapeutic agent against several ailments.

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PMID: 

Pharmacol Rep. 2018 Oct ;70(5):863-874. Epub 2018 Mar 26. PMID: 30092416

Abstract Title: 

Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery.

Abstract: 

BACKGROUND: Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms.METHODS: Tension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab.RESULTS: Kaempferol (10-10M) caused concentration-dependent relaxation (E124.33±4.37%; pD5.03±0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (E55.53±7.72%) in 60mMKpre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (E71.68±11.84%) the relaxation response. However, glibenclamide, BaCl, 4-AP (1mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10mM) and 4-AP (5mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (E94.92±19.60%) in presence of ODQ. H89 significantly decreased (E98.38±8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K(80mM)-depolarized arterial rings, kaempferol (10μM) markedly reduced CaCl-induced contractions (E35.14±6.53% vs. control 69.04±15.19%).CONCLUSION: Kaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BKchannel, sGC, PKA pathways and inhibition of Ca-influx through L-type calcium channels.

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PMID: 

Planta Med. 2017 Jul ;83(10):837-845. Epub 2017 Feb 20. PMID: 28219095

Abstract Title: 

Kaempferol Attenuates Cardiac Hypertrophy via Regulation of ASK1/MAPK Signaling Pathway and Oxidative Stress.

Abstract: 

Kaempferol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperlipidemia, and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains to be elucidated. The aim of our study was to investigate the effects of kaempferol on cardiac hypertrophy and the underlying mechanism. Mice subjected to aorta banding were treated with or without kaempferol (100 mg/kg/d, p. o.) for 6 weeks. Echocardiography was performed to evaluate cardiac function. Mice hearts were collected for pathological observation and molecular mechanism investigation. H9c2 cardiomyocytes were stimulated with or without phenylephrine forstudy. Kaempferol significantly attenuated cardiac hypertrophy induced by aorta banding as evidenced by decreased cardiomyocyte areas and interstitial fibrosis, accompanied with improved cardiac functions and decreased apoptosis. The ASK1/MAPK signaling pathways (JNK1/2 and p38) were markedly activated in the aorta banding mouse heart but inhibited by kaempferol treatment. Inexperiments, kaempferol also inhibited the activity of ASK1/JNK1/2/p38 signaling pathway and the enlargement of H9c2 cardiomyocytes. Furthermore, our study revealed that kaempferol could protect the mouse heart and H9c2 cells from pathological oxidative stress. Our investigation indicated that treatment with kaempferol protects against cardiac hypertrophy, and its cardioprotection may be partially explained by the inhibition of the ASK1/MAPK signaling pathway and the regulation of oxidative stress.

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PMID: 

Curr Drug Discov Technol. 2019 ;16(2):198-203. PMID: 29521239

Abstract Title: 

Hypnotic Effect of Portulaca oleracea on Pentobarbital-Induced Sleep in Mice.

Abstract: 

OBJECTIVE: In Iranian Traditional Medicine, the herbs with cold and wet temperament can help to improve insomnia. Portulaca oleracea has a cold and wet temperament, so the present study was carried out to investigate the sleep-prolonging effect of Portulaca oleracea.METHODS: This work was an experimental study on mice which were randomly divided into these groups: saline (control); Diazepam: positive control); hydro-alcoholic extract of Portulaca oleracea (12.5, 25, 50, 75 and 100 mg/kg) by Soxhlet apparatus and maceration; in the effective (dose25 mg/kg), different fractions of extract were tested. Ethyl acetate fraction (EAF:); N hexane fraction (n-HF); water fraction (WF). All the test compounds were injected intraperitoneally (IP) 30 minutes before pentobarbital administration (30 mg/kg). Duration and latency of pentobarbital-induced sleep were recorded. Also, LD50 of Portulaca oleracea extract was determined and the possible neurotoxicity of the extract was tested on neural PC12 cells. Besides, 30 min after administration of hydroalcoholic extract (HAE) motor coordination (rota-rod test) was assessed.RESULTS: HAE increased the duration of pentobarbital-induced sleep at doses of 25, 50, 75 and 100 mg/kg. The hypnotic effect of HAE was comparable to that induced by diazepam. Similarly, WF, EAF, and NHF at 25 mg/kg could increase sleep duration. The sleep latency was decreased by HAE and NHF but not by WF and EAF. The LD50 value for HAE was found to be 4.8 g/Kg. HAE and its fractions did not show neurotoxic effect in cultured PC12-cell line, also HAE did not affect the animals performance on the rotarod test.CONCLUSION: The present data demonstrated that Portulaca oleracea potentiates sleeping behaviors. The main components responsible for the hypnotic effects of this plant is most likely a non-polar agents which is found in NHF. Isolation of the active constituents may yield a novel sedative drug.

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PMID: 

Nutrients. 2019 Feb 14 ;11(2). Epub 2019 Feb 14. PMID: 30769910

Abstract Title: 

HM-Chromanone Isolated fromL. Protects INS-1 Pancreaticβ Cells against Glucotoxicity-Induced Apoptosis.

Abstract: 

In this study, we investigated whether ()-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone, a homoisoflavonoid compound isolated fromL., protects INS-1 pancreaticβ cells against glucotoxicity-induced apoptosis. Treatment with high glucose (30 mM) induced apoptosis in INS-1 pancreatic β cells; however, the level of cell viability was significantly increased by treatment with ()-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone. Treatment with 10⁻20 µM of ()-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone dose-dependently increased cell viability and significantly decreased the intracellular level of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide levels in INS-1 pancreaticβ cells pretreated with high glucose. These effects were associated with increased anti-apoptotic Bcl-2 protein expression, while reducing pro-apoptotic Bax, cytochrome C, and caspase 9 protein expression. Treatment with ()-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone reduced the apoptosis previously induced by high-level glucose-treatment, according to annexin V/propidium iodide staining. These results demonstrate that ()-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone may be useful as a potential therapeutic agent to protect INS-1 pancreaticβ cells against high glucose-induced apoptosis.

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PMID: 

CNS Neurol Disord Drug Targets. 2019 ;18(4):342-349. PMID: 30868971

Abstract Title: 

Attenuating Effect of Portulaca oleracea Extract on Chronic Constriction Injury Induced Neuropathic Pain in Rats: An Evidence of Anti-oxidative and Anti-inflammatory Effects.

Abstract: 

BACKGROUND: Neuropathic pain responds poorly to drug treatments. The present study investigated the therapeutic effect of Portulaca oleracea, in chronic constriction injury (CCI)-induced neuropathic pain in rats.OBJECTIVE & METHODS: Neuropathic pain was performed by putting four loose ligatures around the sciatic nerve. CCI resulted in the development of heat hyperalgesia, mechanical allodynia and cold allodynia accompanied by an increase in the contents of TNF-α, IL1β, malondialdehyde, with a reduction in total thiol content.RESULTS: Administration of Portulaca oleracea (100 and 200 mg/kg intraperitoneal) for 14 days in CCI rats significantly alleviated pain-related behaviors, oxidative damage and inflammatory cytokines in a dose-dependent manner.CONCLUSION: In conclusion, it is suggested that the antinociceptive effects of Portulaca oleracea might be due to antioxidant and anti-inflammatory properties.

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