The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells

Choi, Eun Joo; Choi, Hyo‐Kyoung; Park, Jae-Ho; Chung, Min‐Yu

doi:10.3390/foods10020408

Cited by 13 publications

(5 citation statements)

References 45 publications

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“…PCSK 9 mediates LDL-R degradation and interferes with its receptor recycling. 7,20 Although the triterpenoids showed no significant differences in the levels of expressed PCSK 9 mRNA expression levels, LDL-R regulation can still occur via the LDL-R/SREBP-2 pathway. It is also worth noting that the tested triterpenoids did not only show the potential to inhibit HMGCR activity but also downregulated the expression of the HMGCR gene in the HepG2 cells, further confirming the potential of AR-5 and ARM-2 as drugs for the control of cholesterol metabolism.…”

Section: ■ Discussionmentioning

confidence: 99%

Triterpenoids from Protorhus longifolia Exhibit Hypocholesterolemic Potential via Regulation of Cholesterol Biosynthesis and Stimulation of Low-Density Lipoprotein Uptake in HepG2 Cells

Ndlovu,

Serem,

Selepe

et al. 2023

ACS Omega

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The increasing incidence of hypercholesterolemia-related diseases even in the presence of the currently available cholesterol-lowering drugs indicates a need to discover new therapeutic drugs. This study aimed to investigate the hypocholesterolemic potential of two triterpenoids isolated from Protorhus longifolia stem bark. In silico techniques and in vitro enzyme assays were used to evaluate the potential inhibition of cholesterol esterase and HMG-CoA reductase by the triterpenoids (ARM-2 and RA-5). The toxicity, modulation of low-density lipoprotein (LDL) uptake, and associated gene expression were determined in HepG2 hepatocytes. In silico molecular docking revealed that ARM-2 compared with RA-5 has a relatively stronger binding affinity for both enzymes. Both triterpenoids further demonstrated promising in silico drug-likeness properties and favorable ADMET profiles characterized by high intestinal absorption and lack of CYP450 enzyme inhibition. The compounds further showed, to varying degrees of efficacy, inhibition of cholesterol micellization as well as both cholesterol esterase and HMG-CoA reductase activities with IC50 values ranging from 16.4 to 41.1 μM. Moreover, enhanced hepatic cellular LDL uptake and the associated upregulation of the LDL-R and SREBP-2 gene expression were observed in the triterpenoid-treated HepG2 cells. It is evident that the triterpenoids, especially ARM-2, possess hypocholesterolemic properties, and these molecules can serve as leads or structural templates for the development of new hypocholesterolemic drugs.

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Section: ■ Discussionmentioning

confidence: 99%

Triterpenoids from Protorhus longifolia Exhibit Hypocholesterolemic Potential via Regulation of Cholesterol Biosynthesis and Stimulation of Low-Density Lipoprotein Uptake in HepG2 Cells

Ndlovu,

Serem,

Selepe

et al. 2023

ACS Omega

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“…The positive effects of Capsella bursa-pastoris on the hemorrhoidal disease-related symptoms and the physical examination findings have been noted in the literature and attributed to its anti-oxidant and anti-inflammatory properties. 12 Additionally, it was reported that Capsella bursa-pastoris plays a role in the biosynthesis of several active substances, including tannins, sulforaphanes, tyramines, sterols, flavonoids, choline, acetylcholine, and histamine. 3,20,25 Apaydin Yildirim et al 3 demonstrated the anti-hemorrhoidal effects of ethanol and water extracts of Capsella bursapastoris on croton oil-induced hemorrhoids in rats.…”

Section: Discussionmentioning

confidence: 99%

Impact of Capsella bursa-pastoris (Shepherd’s Purse) Herbal Tea Preparations on Symptoms and Severity of Hemorrhoidal Disease: A Prospective Randomized Study

Mert

YİĞİT

2022

International Journal of Traditional and Complementary Medicine Research

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Objective: Medicinal herbs have been used to treat hemorrhoidal diseases since old times. Given its anti-oxidant and anti-inflammatory mechanisms, Capsella bursa-pastoris (Shepherd’s purse) may potentially lead to regression of the hemorrhoidal plexuses. In this context, the objective of this study is to investigate the effect of Shepherd’s purse on the severity and physical examination findings of hemorrhoidal disease in patients. Materials-Methods: The patients were randomized into two groups: the control group (conservative treatment only for three months), and the study group (conservative treatment and Shepherd’s purse for three months). Results: The study sample consisted of a total of 218 patients who were randomized into the study and control groups, with 109 patients in each group. The mean age of the patients in the patient and control groups were 35.5±11.7 and 39.5±14.6, respectively, referring to a significant difference between the groups (p=0.030). At the 3rd-month follow-up examination, it was determined that there were significantly fewer patients with bleeding and difficulty during defecation in the study group compared to the control group (p=0.001). Patients in the study group had significantly lower VAS scores for pain and the number of affected quadrants compared to the control group (p

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“…It was widely demonstrated that various natural products reduced the gene expression of PCSK9. For example, extracts prepared from welsh onion, shepherd’s purse, pigeon pea, and black raspberry produced a significant reduction in PCSK9 gene expression [ 42 , 43 , 44 , 45 ]. Interestingly, all these three extracts concomitantly induced the expression of LDL-R as well as the uptake of LDL-C by liver cells.…”

Section: Discussionmentioning

confidence: 99%

Acanthaster planci Inhibits PCSK9 and Lowers Cholesterol Levels in Rats

et al. 2021

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Atherosclerosis is the main cause of cardiovascular diseases which in turn, lead to the highest number of mortalities globally. This pathophysiological condition is developed due to a constant elevated level of plasma cholesterols. Statin is currently the widely used treatment in reducing the level of cholesterols, however, it may cause adverse side effects. Therefore, there is an urgent need to search for new alternative treatment. PCSK9 is an enzyme responsible in directing LDL-receptor (LDL-R)/LDL-cholesterols (LDL-C) complex to lysosomal degradation, preventing the receptor from recycling back to the surface of liver cells. Therefore, PCSK9 offers a potential target to search for small molecule inhibitors which inhibit the function of this enzyme. In this study, a marine invertebrate Acanthaster planci, was used to investigate its potential in inhibiting PCSK9 and lowering the levels of cholesterols. Cytotoxicity activity of A. planci on human liver HepG2 cells was carried out using the MTS assay. It was found that methanolic extract and fractions did not exhibit cytotoxicity effect on HepG2 cell line with IC50 values of more than 30 µg/mL. A compound deoxythymidine also did not exert any cytotoxicity activity with IC50 value of more than 4 µg/mL. Transient transfection and luciferase assay were conducted to determine the effects of A. planci on the transcriptional activity of PCSK9 promoter. Methanolic extract and Fraction 2 (EF2) produced the lowest reduction in PCSK9 promoter activity to 70 and 20% of control at 12.5 and 6.25 μg/mL, respectively. In addition, deoxythymidine also decreased PCSK9 promoter activity to the lowest level of 60% control at 3.13 μM. An in vivo study using Sprague Dawley rats demonstrated that 50 and 100 mg/kg of A. planci methanolic extract reduced the total cholesterols and LDL-C levels to almost similar levels of untreated controls. The level of serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) showed that the administration of the extract did not produce any toxicity effect and cause any damage to rat liver. The results strongly indicate that A. planci produced a significant inhibitory activity on PCSK9 gene expression in HepG2 cells which may be responsible for inducing the uptake of cholesterols by liver, thus, reducing the circulating levels of total cholesterols and LDL-C. Interestingly, A. planci also did show any adverse hepato-cytotoxicity and toxic effects on liver. Thus, this study strongly suggests that A. planci has a vast potential to be further developed as a new class of therapeutic agent in lowering the blood cholesterols and reducing the progression of atherosclerosis.

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The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells

Cited by 13 publications

References 45 publications

Triterpenoids from Protorhus longifolia Exhibit Hypocholesterolemic Potential via Regulation of Cholesterol Biosynthesis and Stimulation of Low-Density Lipoprotein Uptake in HepG2 Cells

Triterpenoids from Protorhus longifolia Exhibit Hypocholesterolemic Potential via Regulation of Cholesterol Biosynthesis and Stimulation of Low-Density Lipoprotein Uptake in HepG2 Cells

Impact of Capsella bursa-pastoris (Shepherd’s Purse) Herbal Tea Preparations on Symptoms and Severity of Hemorrhoidal Disease: A Prospective Randomized Study

Acanthaster planci Inhibits PCSK9 and Lowers Cholesterol Levels in Rats

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