Optimization of ultrasound-assisted extraction of Acalypha indica using box-behnken design: Network pharmacology, molecular docking, and evaluation of antidiabetic activity
This study aimed to optimize the ultrasound-assisted extraction (UAE) of Acalypha indica to maximize total phenolic content (TPC) and total flavonoid content (TFC), key contributors to its antidiabetic activity. Initial one-factor-at-a-time (OFAT) screening identified extraction temperature (ET), ultrasonication time (UT), and solid-to-solvent ratio (SLR) as significant parameters. These were further optimized using Box-Behnken Design (BBD) and Response Surface Methodology (RSM), yielding optimal conditions of 60°C, 30 minutes, and 20 g/mL. Under these conditions, TPC and TFC were 93.22 mg GAE/g and 27.82 mg QE/g, respectively, closely matching predicted values. The optimized UAE extract demonstrated significant α-amylase (IC50 50.43 μg/mL) and α-glucosidase (IC50 53.99 μg/mL) inhibition, supporting its antidiabetic potential. Network pharmacology analysis identified critical pathways including PI3K-Akt, MAPK, and insulin resistance, with key targets such as TLR4, STAT3, IGF1R, and PIK3R1 involved in glucose regulation. Molecular docking against human pancreatic α-amylase (4W93) and maltase-glucoamylase (3TOP) showed that acarbose had the strongest inhibition, while quercetin and kaempferol exhibited notable binding affinities, suggesting potential as natural enzyme inhibitors. Overall, this study establishes an optimized UAE protocol for Acalypha indica, integrating experimental and computational approaches, highlighting its antidiabetic efficacy, and providing a foundation for further pharmacological validation and formulation development.
- Research Article
30
- 10.1016/j.jarmap.2022.100369
- Jan 12, 2022
- Journal of Applied Research on Medicinal and Aromatic Plants
Optimization of extraction method for Kleeb Bua Daeng formula and comparison between ultrasound-assisted and microwave-assisted extraction
- Research Article
10
- 10.1016/j.jafr.2024.101312
- Jul 24, 2024
- Journal of Agriculture and Food Research
Optimising ultrasound-assisted extraction conditions for maximising phenolic, flavonoid content and antioxidant activity in hog plum peel and seed: A response surface methodology approach
- Research Article
20
- 10.3390/plants12132455
- Jun 26, 2023
- Plants
This study optimized ultrasound-assisted extraction conditions to maximize the extraction yield, total flavonoid content (TFC), total phenolic content (TPC), and DPP IV enzyme inhibitory activity from Moringa oleifera. The four UAE factors, solvent ratio (A), solvent–solid ratio (B), extraction temperature (C), and extraction time (D), were optimized using response surface methodology (RSM). A Box–Behnken design was used for the experimental design. The optimal conditions were found to be a 50% v/v solvent ratio, a 30% v/w solvent–solid ratio, 35 °C extraction temperature, and 45 min extraction time. The experimental value of extraction yield (R1), TFC (R2), TPC (R3), and DPP IV enzyme inhibitory activity (R4) (87.99% w/w, 56.63 mg QE/g extract, 97.26 mg GAE/g extract, and 93.32% inhibition, respectively) agreed with those predicted by RSM models (88.10% w/w, 56.61 mg QE/g extract, 97.16 mg GAE/g extract, and93.38% inhibition, respectively), thus demonstrating the appropriateness of the model used and the ability of the RSM to optimize the extraction conditions. Excellent DPP IV enzyme inhibitory activity was exhibited by M. oleifera compared with the standard, sitagliptin. While the modeled equation fits the data, the t-test is not significant, suggesting that the experimental values agree with those predicted by the RSM–BBD
- Research Article
3
- 10.1016/j.microc.2024.111080
- Jun 27, 2024
- Microchemical Journal
RSM-based optimization of microwave- and ultrasound-assisted green extraction of iron-chelating and antioxidant natural products from Azadirachta indica leaves
- Research Article
8
- 10.3390/foods14020291
- Jan 17, 2025
- Foods (Basel, Switzerland)
Centella asiatica (CA), known for its health-promoting properties, is rich in bioactive compounds. This study optimised ultrasound-assisted extraction (UAE) parameters to maximise total phenolic content (TPC) and total flavonoid content (TFC) using the response surface methodology (RSM). Ethanol concentration and solvent volume significantly influenced TPC and TFC yields (p < 0.0001), while ultrasonic power had nonsignificant effects (p < 0.05). Time showed no significant effect on TPC (p > 0.05) but influenced TFC due to flavonoids' sensitivity to degradation (p < 0.05). Variable interactions were negligible (p > 0.05). The relationship between responses (TPC and TFC) and independent parameters could be expressed as the quadratic models fitted with a Predicted R2 of 0.8263 for TPC and 0.9006 for TFC. Based on RSM, the optimal conditions-75% ethanol concentration, 87.5 W ultrasonic power, 30 min extraction time, and 20 mL solvent volume-yielded TPC and TFC values of 52.29 ± 1.65 mg/g and 43.71 ± 1.92 mg/g, closely aligning with model predictions at 95% confidence. Additionally, the optimal UAE condition provided asiaticoside of 37.56 ± 4.25 mg/g and madecassoside of 16.91 ± 1.28 mg/g. This study offers valuable insights into the factors influencing UAE efficiency, sustainability, and scalability for recovering bioactive compounds, underscoring its potential as a sustainable method for developing functional food ingredients from CA.
- Research Article
- 10.1007/s13596-020-00539-2
- Jan 28, 2021
- Advances in Traditional Medicine
The selection of appropriate conditions for increasing the extraction efficiency is important. The response surface method (RSM) is a statistical and mathematical technique which it can be used to examine the dependence between the responses with variables in a process and also determine the optimal conditions. In this study, the experimental design of General full factorial (GFF) was used by Minitab 17 software. The variables were time (30, 60 and 90 min), solvent (water, methanol and n-hexane) and method (maceration and ultrasound-assisted extraction). The main effects and also interaction terms were investigated on amounts of total phenolic content (TPC), total flavonoid content (TFC) and the antioxidant activity (according to DPPH, FRAP, IC50 and BCB) of extract of Arenaria hispanica L.. A multiple regression, first degree model was used to express the responses. An analysis of variance (ANOVA) with 95% confidence level was then carried out for each response (TPC, TFC, FRAP, IC50 and BCB) in order to test the model significance and suitability. In optimum conditions, the maceration method was optimum method for TPC, FRAP and BCB, while for TFC was ultrasound-assisted extraction. Water was optimal solvent for TPC, FRAP and BCB, but methanol was obtained as the best solvent for TFC and IC50. Also, the extraction time of TPC was 60 min and for TFC, IC50, FRAP and BCB obtained 30 min. The mounts of TPC, TFC, IC50, FRAP and BCB in the optimum conditions obtained 173.93 ± 0.50 (mg GAE/g extract), 184.27 ± 4.04 (mg QC/g extract), 0.69 ± 0.03 (mg/mL), 734.80 ± 2.02 (mmol Fe2+/g exctract) and 21.23 ± 0.22; respectively.
- Research Article
10
- 10.3390/molecules28020487
- Jan 4, 2023
- Molecules
This study presents modeling and optimization of ultrasound-assisted extraction (UAE) of Melastoma malabathricum with the objective of evaluating its phytochemical properties. This one-factor-at-a-time (OFAT) procedure was conducted to screen for optimization variables whose domains included extraction temperature (XET), ultrasonic time (XUT), solvent concentration (XSC), and sample-to-liquid ratio (XSLR). Response surface methodology (RSM) coupled with Box–Behnken design (BBD) was applied to establish optimum conditions for maximum antioxidant extraction. Modeling and optimization conditions of UAE at 37 kHz, XET 32 °C for XUT 16 min and dissolved in an XSC 70% ethanol concentration at a XSLR 1:10 ratio yielded scavenging effects on 2,2-diphenyl-1-picryl-hydrazyl (DPPH) at 96% ± 1.48 and recorded values of total phenolic content (TPC) and total flavonoid content (TFC) at 803.456 ± 32.48 mg GAE (gallic acid equivalents)/g, and 102.972 ± 2.51 mg QE (quercetin equivalents)/g, respectively. The presence of high flavonoid compounds was verified using TWIMS-QTOFMS. Chromatic evaluation of phytochemicals using gas chromatography–mass spectrometry (GC–MS) revealed the presence of 14 phytocompounds widely documented to play significant roles in human health. This study provides a comparative evaluation with other studies and may be used for validation of the species’ potential for its much-acclaimed medicinal and cosmeceutical uses.
- Research Article
23
- 10.1080/07315724.2018.1524315
- Dec 27, 2018
- Journal of the American College of Nutrition
Objective: This investigation was undertaken to optimize the effective extraction of total phenolics content (TPC), total flavonoids content (TFC), and antioxidant activity from the Mucuna macrocarpa (MM) beans. An ultrasound-assisted extraction (UAE) technique with water as an effective solvent was proposed for the response surface methodology (RSM) optimization.Methods: A three-level, two-factor central composite design (CCD) was employed to reveal the optimal points of variables. Different extraction times (5, 10, 15 minutes) and ultrasonic power levels (10, 20, 30 W) were used for the optimization. The experimental runs given by the RSM were evaluated for TPC, TFC, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (RSA), and N,N-dimethyl-p-phenylenediamine (DMPD) RSA and ferric reducing antioxidant power (FRAP).Results: The predicted times for maximum extraction of TPC (186.61 mg GAE g−1), TFC (148.87 mg QUE g−1), and DPPH RSA (99.37%), and DMPD RSA (50.58%) and FRAP (2.38 O.D. at 593 nm) were 12.57, 12.84, 12.43, 12.97, and 13.24 min, and ultrasonic power levels were found to be 27.30, 26.76, 26.22, 27.03, and 27.84 W, respectively. Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis of phenolics compounds from the RSM optimized sample showed tannic acid (48.09 ± 1.92 mg/g), gallic acid (1.17 ± 0.19 mg/g), p-coumaric acid (0.56 ± 0.03 mg/g), and p-hydroxybenzoic acid (0.049 ± 0.01 mg/g) content.Conclusion: Water and ultrasonication were found to be an effective extraction solvent and technique. RSM was effectively employed to investigate the optimal process conditions for the maximum extraction of TPC, TFC, and antioxidant compounds from the MM beans. Further, MM beans can be explored as a prominent antioxidant source for the treatment of several disorders.
- Research Article
5
- 10.1002/cbdv.202401337
- Nov 18, 2024
- Chemistry & biodiversity
The current work aims to optimize the ultrasound-assisted extraction (UAE) of Cistus salviifolius L. (aerial parts) antioxidative phenolic compounds using response surface methodology. A Box-Behnken design has been conducted to investigate the effect of four factors, namely: (i) percentage of ethanol (50-90 %, v/v), (ii) temperature (40-80 °C), (iii) solvent-solid ratio (10-50 mL g-1) and (iv) extraction time (5-25 min) on four responses, namely: total phenolic content (TPC), total flavonoid content (TFC) 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical inhibition, and ferric reducing antioxidant power (FRAP). Based on the desirability index, UAE with 50 % (v/v) ethanol, at 80 °C, using a solvent-solid ratio of 32.24 mL g-1, for 21 min resulted in the maximum recovery of phenolic antioxidants. Under optimum conditions, the experimental values of TPC, TFC, % DPPH radical scavenging activity, and FRAP were 171.67±4.69 mg GAE g-1, 26.87±0.78 mg CE g-1, 81.31±0.16 %, and 1038.22±7.69 μmol TE g-1, respectively. Results shows a reasonable agreement of experimental values with the predicted ones; the absolute error values being in all cases lower than 2.90 %. The present work provide a developed eco-friendly extarction method that is appropriate for the improved recovery of phenolic antioxidants from C. salviifolius L.
- Research Article
118
- 10.1016/j.indcrop.2016.01.010
- Feb 8, 2016
- Industrial Crops and Products
Ultrasound assisted extraction of total phenolics from Cassia auriculata leaves and evaluation of its antioxidant activities
- Research Article
37
- 10.1016/j.ultsonch.2022.106017
- Apr 28, 2022
- Ultrasonics Sonochemistry
A novel strategy for producing nano-particles from date seeds and enhancing their phenolic content and antioxidant properties using ultrasound-assisted extraction: A multivariate based optimization study
- Research Article
15
- 10.1007/s10068-022-01150-8
- Sep 2, 2022
- Food Science and Biotechnology
A Box–Behnken Design (BBD) was employed to optimize the extraction of antioxidants from Ruby S apple peel by ultrasound-assisted extraction (UAE). The effect of extraction temperature (20–40 °C), extraction time (15–45 min), and ethanol concentration (50–90%) in water on extraction yield, total phenol content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity of Ruby S peel extracts (RPEs) were investigated. The optimized extraction conditions that maximized extraction yield, TPC, TFC, and DPPH radical scavenging ability, were temperature 20 °C, extraction time 25.30 min, and ethanol concentration 50%. The validity of designed model was verified, and experimental values obtained under optimum conditions concurred with predicted values. Hyperoside, isoquercitrin, and phloridzin, were among the major flavonoids extracted. Our findings demonstrate the suitability of UAE and RSM for the optimization of Ruby S peel extraction and suggest the potential use of RPEs as bioactive functional materials.
- Research Article
- 10.9734/ajraf/2023/v9i4249
- Nov 3, 2023
- Asian Journal of Research in Agriculture and Forestry
Aims: Plants need an appropriate amount of nutrients such as copper for growth and development. However, excess of copper may interrupt plant development and cause stress that led to biochemical compounds being synthesized. The influence of a high copper sulfate concentration on phenolic and flavonoid content in Phyllanthus tenellus plants was investigated.
 Place and Duration of Study: The experiment was conducted in a government compound at MARDI Serdang, Selangor, Malaysia (2° 59' 31.7292'' N 101° 41' 56.706'' E), from April 2021 to Jun 2021.
 Methodology: The experiment was conducted using a vertical column planting system under a side-netted rain shelter. The plants were subjected to 0.5 M copper sulfate sprayed after 60 days of planting and harvested 0.5, 1.5, 3, 6, 12 and 24 h after sprayed for further analysis. Total phenolic content was calculated as mg gallic acid equivalent and total flavonoid content was measured as quercetin equivalent.
 Results: Highest total phenolic and flavonoid content was detected after 0.5 hours of copper sulfate application and started to decrease towards 24 hours after sprayed. Treated samples showed a 1.18-fold increase in total phenolic content and 1.4-fold increase in total flavonoid content compared to control untreated samples after 0.5 hours of sprayed. Control samples showed stability in both total phenolic and flavonoid content throughout the harvesting periods. Phenolic is the major secondary metabolites in Phyllanthus tenellus plants.
 Conclusion: Data revealed that the application of 0.5 M copper sulfate is able to enhance total phenolic and flavonoid content in Phyllanthus tenellus plants. The study suggested that the optimum harvesting time is 0.5 hours after copper sulfate application.
- Research Article
3
- 10.38150/sajeb.4(5).p261-266
- Jan 20, 2015
- South Asian Journal of Experimental Biology
The focus of the present study was to determine the association of the anti-oxidant activity of Costus speciosus (Koen Ex. Retz.) Sm. with the total phe-nolic content and the total flavonoid content. The antioxidant activity of the extracts was quantified by diphenylpicrylhydrazyl (DPPH) assay. The total phenolic content was determined by the Folin-Ciocalteau method and the total flavonoid content was determined by the aluminium chloride method. Among the four extracts of the plant, the ethanol extract exhibited the high-est antioxidant activity and also the highest total phenolic and flavonoid con-tents. A strong correlation was observed between the antioxidant activity and the total phenolic and flavonoid contents. A statistical model was de-rived to explain this dependence and a non-linear association was observed between the antioxidant activity and the total flavonoid content.
- Research Article
28
- 10.1080/01496395.2020.1781894
- Jun 24, 2020
- Separation Science and Technology
Deep eutectic solvent (DES) was synthesized using choline chloride/glycerol for the extraction of ethnomedicinal compounds from Cymbopogon citratus by maceration and ultrasound-assisted extraction (UAE). The optimization of extraction parameters and their interactive influence were evaluated by response surface methodology. Extracts were characterized using different antioxidant and antimicrobial activities. Different phenolics/flavonoids were identified by LC-ESI-MS. The significantly enhanced extraction yield was obtained using DES in comparison with aq. methanol. Higher values of TPC, TFC, and DPPH inhibition were obtained (135 mg GAE/g, 91 mg QE/g, and 93%, respectively) for DES by applying UAE as compared to maceration. Abbreviations: DES: Deep eutectic solvent; ChCl:Gly: Choline chloride: glycerol; UAE: Ultrasound-assisted extraction; TPC: Total phenolic content; TFC: Total flavonoids content; DPPH: 2, 2-diphenyl-1- picrylhydrazyl; RSM: Response surface methodology; ANOVA: Analysis of variance; BBD: Box-Behnken design; C.V: Coefficient of variation; MIC: Minimum inhibitory concentration; LC-ESI-MS: Liquid chromatography-electron spray ionization-mass spectroscopy
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