The inhibitory effects of an eight-herb formula (RCM-107) on pancreatic lipase: enzymatic, HPTLC profiling and in silico approaches

Luo, Shiqi; Gill, Harsharn; Dias, Daniel A.; Li, Mingdi; Hung, Andrew; Nguyen, Linh Toan; Lenon, George Binh

doi:10.1016/j.heliyon.2019.e02453

Cited by 14 publications

(12 citation statements)

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“…Their protein structure affords a high level of druggability and target validation which makes enzymes an attractive target for novel drug discovery efforts [ 3 ]. Enzyme inhibitors form an important class of clinical drugs ranging in use from cancer [ 4 , 5 ], cardiovascular disease [ 6 , 7 ], diabetes [ 8 , 9 ], neurological disorders [ 10 – 13 ] and obesity [ 14 , 15 ]. Inhibitors of the endogenous carbohydrases α-glucosidase and α-amylase, reduces postprandial hyperglycaemia by delaying the digestion of dietary carbohydrates and are valuable therapeutics in the management of diabetes [ 8 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays

et al. 2021

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Background Enzyme assays have widespread applications in drug discovery from plants to natural products. The appropriate use of blanks in enzyme assays is important for assay baseline-correction, and the correction of false signals associated with background matrix interferences. However, the blank-correction procedures reported in published literature are highly inconsistent. We investigated the influence of using different types of blanks on the final calculated activity/inhibition results for three enzymes of significance in diabetes and obesity; α-glucosidase, α-amylase, and lipase. This is the first study to examine how different blank-correcting methods affect enzyme assay results. Although assays targeting the above enzymes are common in the literature, there is a scarcity of detailed published protocols. Therefore, we have provided comprehensive, step-by-step protocols for α-glucosidase-, α-amylase- and lipase-inhibition assays that can be performed in 96-well format in a simple, fast, and resource-efficient manner with clear instructions for blank-correction and calculation of results. Results In the three assays analysed here, using only a buffer blank underestimated the enzyme inhibitory potential of the test sample. In the absorbance-based α-glucosidase assay, enzyme inhibition was underestimated when a sample blank was omitted for the coloured plant extracts. Similarly, in the fluorescence-based α-amylase and lipase assays, enzyme inhibition was underestimated when a substrate blank was omitted. For all three assays, method six [Raw Data - (Substrate + Sample Blank)] enabled the correction of interferences due to the buffer, sample, and substrate without double-blanking, and eliminated the need to add substrate to each sample blank. Conclusion The choice of blanks and blank-correction methods contribute to the variability of assay results and the likelihood of underestimating the enzyme inhibitory potential of a test sample. This highlights the importance of standardising the use of blanks and the reporting of blank-correction procedures in published studies in order to ensure the accuracy and reproducibility of results, and avoid overlooked opportunities in drug discovery research due to inadvertent underestimation of enzyme inhibitory potential of test samples resulting from unsuitable blank-correction. Based on our assessments, we recommend method six [RD − (Su + SaB)] as a suitable method for blank-correction of raw data in enzyme assays.

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Section: Introductionmentioning

confidence: 99%

Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays

et al. 2021

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“…Our recent work has demonstrated potent pancreatic lipase inhibitory effect of this formula, which may lead to a decrease of lipid absorption, thus weight loss. Also, we have identified the presence of six active chemical compounds in RCM-107 and related single herbs, such as EGCG, epicatechin-3-gallate (ECG), (-)-epicatechin (EC), caffiene, rutin and crocin [21]. However, to date there is no published scientific evidence indicating the effects of the RCM-107 and its individual herbal ingredients on pancreatic alpha-amylase activity.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of a weight-loss Chinese herbal formula RCM-107 on pancreatic α-amylase activity: Enzymatic and in silico approaches

et al. 2020

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Reducing carbohydrates digestion by having a low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107 (Slimming Plus), an eight-herb formula that is modified from RCM-104, indicated significant weight-loss action in clinical trials. However, no published research has studied its mechanism of action on reducing carbohydrate absorption via suppressing the activities of porcine pancreatic alpha-amylase (PPA). In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact. Therefore, our data has provided new knowledge on the mechanisms of action of the RCM-107 formula and its individual herbal ingredients for weight loss, in terms of decreasing carbohydrate digestion via the inhibition of pancreatic alpha-amylase.

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“…There are various approaches to reduce weight, including decreasing nutrition absorption or suppressing appetite [4]. Glucagon-like peptide-1(GLP-1) is one of the "satiety signals" that reduces concentration of 0.05 and 0.1mg/mL (p < 0.0001; p < 0.005).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, we have preliminary data suggesting that there are amylase inhibition effects of this formula that reduce carbohydrate digestion. We have also identified the presence of six active chemical compounds in RCM-107 and related single herbs, such as EGCG, epicatechin-3-gallate (ECG), (−)-epicatechin (EC), caffiene, rutin and crocin [4]. However, to our knowledge, no published scientific data describes the effects of RCM-107 and its eight ingredients on GLP-1 secretion.Given this lack of information, this present study aims to firstly determine the effects of RCM-107 and its individual ingredients on GLP-1 secretion in NCI-H716 cells using the enzyme-linked immunosorbent assay (ELISA).…”

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confidence: 98%

“…Juzep./Ze xie; Plantaginis semen/Plantago asiatica L./Che qian zi; Cassiae semen/Cassia obtusifolia L./Jue ming zi; Sophorae flos/Sophora japonica L./ Huai hua; and Gardeniae fructus/Gardenia jasminoides Ellis./Zhi zi [14]. Our recent work has demonstrated the potent pancreatic lipase inhibitory effect of this formula, which can lead to decreased lipid absorption and, thus, potentially weight loss [4]. In addition, we have preliminary data suggesting that there are amylase inhibition effects of this formula that reduce carbohydrate digestion.…”

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confidence: 99%

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The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion—An In Vitro and In Silico Study

Luo

Gill

Feltis

et al. 2020

IJMS

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Obesity is a multifactorial disease that can lead to other health issues. Glucagon-like peptide-1(GLP-1), as one of the satiety signal, has been linked with appetite suppression and weight loss. Due to the limitations of GLP-1 and its analogues, alternative treatments such as herbal therapies have become popular. The herbal formula RCM-107 has demonstrated its inhibitory effects on lipid and carbohydrate absorption in our previous work. However, no published data described its effects on GLP-1 secretion. Therefore, this study aimed to determine the effects of RCM-107 and its individual ingredients on GLP-1 secretion via enzyme-linked immunosorbent assay (ELISA). Furthermore, molecular docking was performed to predict the key chemical compounds that are likely to be GLP-1 receptor agonists. Gardeniae fructus, one of the ingredients in RCM-107, demonstrated significantly greater effects on inducing GLP-1 secretion than the positive control epigallocatechin gallate (EGCG). Two Gardeniae fructus ligands, 3-epioleanolic acid and crocin were predicted to bind to the active form of GLP-1 receptor at the binding pocket with residues known for the receptor activation, suggesting that they could potentially serve as receptor agonists. Overall, this study reported the effects of researched herbs on GLP-1 secretion and proposed two compounds that may be responsible for antiobesity via GLP-1 receptor activation.Int. J. Mol. Sci. 2020, 21, 2854 2 of 13 hunger. It is known as an incretin hormone, secreted by enteroendocrine L cells in the gastrointestinal tract (GI) [5]. The amount of GLP-1 secretion is in response to calory intake. It can be stimulated by both fats and carbohydrates, while protein has only a minor impact [6]. The existing two major molecular forms of GLP-1 include GLP-1 (7-36) and GLP-1 (7-37), while the circulating active GLP-1 is mainly found in the form of GLP-1(7-36) [7].Reports showed that native GLP-1 has a very short half-life (less than 2 min) in vivo as a result of degradation by dipeptidyl peptidase-4 (DPP-4) in plasma [7,8]. Liraglutide, a stable GLP-1 analogue, was approved by FDA for treating obesity in 2014. It can suppress appetite and increase satiety by activating the GLP-1 receptor, which is located in the hypothalamus, gastrointestinal tract and pancreas. However, it is a daily injectable treatment that is also relatively high cost [6,9].Due to these limitations on GLP-1 and its analogues, cost-effective herbal supplements, including natural products, medicinal plant extracts and Chinese herbal medicine, are popular alternatives for weight reduction. Natural products such as epigallocatechin gallate (EGCG) [5], geniposide [10], berberine [11] and ginsenoside metabolite compound K [12] have been shown to stimulate GLP-1 secretion in in vitro experiments.In this paper, we have investigated the commercially available RCM-107 formula (Slimming Plus), a modification of our previously studied RCM-104 formula, which demonstrated significant effects on weight loss in clinical trials [13]. RCM-107 co...

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The inhibitory effects of an eight-herb formula (RCM-107) on pancreatic lipase: enzymatic, HPTLC profiling and in silico approaches

Cited by 14 publications

References 39 publications

Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays

Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays

Inhibitory effect of a weight-loss Chinese herbal formula RCM-107 on pancreatic α-amylase activity: Enzymatic and in silico approaches

The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion—An In Vitro and In Silico Study

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