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Phytochemical profiling, in vitro antioxidants, and antidiabetic efficacy of ethyl acetate fraction of Lespedeza cuneata on streptozotocin-induced diabetic rats

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Abstract

In the recent past, phytomolecules are exponentially applied in discovering the antidiabetic drug due to less adverse effects. This work screened the active solvent fraction of Lespedeza cuneata based on the phytochemical, enzyme inhibition, and antioxidant properties. The antioxidant efficacy of the different fractions of the L. cuneata was assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing power, hydrogen peroxide, and hydroxyl radical scavenging assays. The digestive enzyme (α-amylase and α-glucosidase) inhibitory activity was also evaluated. The phytochemical composition of ethyl acetate fraction of L. cuneata (Lc-EAF) was studied by UHPLC-QTOF–MS/MS. The effect of Lc-EAF treatments on glucose uptake was studied in insulin resistance HepG2 cells (IR-HepG2). Further, the antidiabetic effect of Lc-EAF in streptozotocin (STZ)-induced diabetic mice were demonstrated. Ethyl acetate, hexane, and methanol fractions of the L. cuneata showed notable antioxidant, α-amylase, and α-glucosidase inhibitory properties. Among the fractions, Lc-EAF was found to be the most potent. The Lc-EAF exhibited an IC50 of 205.32 ± 23.47 µg/mL and 105.32 ± 13.93 µg/mL for α-amylase and α-glucosidase inhibition, respectively. In addition, 75 µg/mL of Lc-EAF exposure enhanced glucose uptake (68.23%) in IR-HepG2 cells. In vivo study indicated that treatment of Lc-EAF (100 mg/kg b.wt) maintained the blood glucose level through reduced insulin level while improving the lipid profile, hepatic, and renal markers. These findings suggest that Lc-EAF could be considered a prominent source for antidiabetic, anti-hyperlipidemic, and anti-ROS potentials.

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Data availability

The data are available from the corresponding author upon reasonable request and with permission of the study sponsor.

Abbreviations

ABTS:

2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

ALT:

Aspartate aminotransferase

B.wt:

Body weight

BUN:

Blood urea nitrogen

DM:

Diabetes mellitus

DNS:

3, 5-Dinitrosalicylic acid

DPPH:

1,1-Diphenyl-2-picrylhydrazyl

GAE:

Gallic acid equivalents

HDL-C:

High-density lipoprotein cholesterol

IP:

Intraperitoneal

IR-HepG2:

Insulin resistance HepG2 cells

Lc-EAF:

Ethyl acetate fractions of L. cuneata

Lc-HF:

Hexane fractions of L. cuneata

Lc-MF:

Methanol fractions of L. cuneata

LDL-C:

Low-density lipoprotein cholesterol

QE:

Quercetin equivalents

STZ:

Streptozotocin

TPC:

Total phenolic content

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Funding

This study was supported by the National Research Foundation of Korea (NRF) (2019R1A1055452; 2021R1I1A1A01057742; 2022R1A2C2091029; 2022R1F1A1063364).

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  1. Arokia Vijaya Anand Mariadoss and SeonJu Park contributed equally to this work.

Authors and Affiliations

  1. Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 200-701, Republic of Korea

    Arokia Vijaya Anand Mariadoss, Kandasamy Saravanakumar, Anbazhagan Sathiyaseelan & Myeong-Hyeon Wang

  2. Department of Orthopaedic Surgery, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, 18450, Republic of Korea

    Arokia Vijaya Anand Mariadoss

  3. Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon, 24341, Republic of Korea

    SeonJu Park

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Contributions

Arokia Vijaya Anand Mariadoss: conceptualization, data curation, formal analysis, investigation, methodology, visualization, roles/writing-original draft, writing-review and editing. SeonJu Park: formal analysis, investigation. Kandasamy Saravanakumar: data curation, formal analysis, validation, review and editing. Anbazhagan Sathiyaseelan: software, formal analysis, data curation, validation. Myeong-Hyeon Wang: funding acquisition, project administration, resources, software, supervision, validation.

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Mariadoss, A.V.A., Park, S., Saravanakumar, K. et al. Phytochemical profiling, in vitro antioxidants, and antidiabetic efficacy of ethyl acetate fraction of Lespedeza cuneata on streptozotocin-induced diabetic rats. Environ Sci Pollut Res 30, 60976–60993 (2023). https://doi.org/10.1007/s11356-023-26412-8

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