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Isolation, characterization, and therapeutic activity of bergenin from marlberry (Ardisia colorata Roxb.) leaf on diabetic testicular complications in Wistar albino rats

  • Sanasam Sanjeev
  • Meesala Krishna Murthy
  • Maibam Sunita Devi
  • Maurya Khushboo
  • Zothanmawii Renthlei
  • Kalibulla Syed Ibrahim
  • Nachimuthu Senthil Kumar
  • Vikas Kumar Roy
  • Guruswami GurusubramanianEmail author
Research Article
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Abstract

Bergenin is one of the phytochemical constituents in marlberry (Ardisia colorata Roxb.) having antioxidant, anti-diabetic, and anti-inflammatory properties. A. colorata has been used as an herbal medicine in Southeast Asia particularly in Northeast India to treat diabetes. Bergenin was isolated from methanol extract of A. colorata leaf (MEACL) by column chromatography and TLC profiling. Characterization and structural validation of bergenin were performed by spectroscopic analyses. A LC-ESI-MS/MS method was developed for the quantitation of bergenin and validated as per the guidelines of FDA and EMA. The validated method was successfully utilized to quantify bergenin concentration in MEACL samples. Therapeutic efficacy of bergenin was investigated on streptozotocin-induced diabetic rats by following standard protocols. Bergenin supplementation significantly improved the physiological and metabolic processes and in turn reverses diabetic testicular dysfunction via increasing serum testosterone concentrations and expression pattern of PCNA, improving histopathological and histomorphometric manifestations, modulating spermatogenic events and germ cell proliferation, restoring sperm quality, reducing sperm DNA damage, and balancing the antioxidant enzymes levels. Hence, A. colorata leaf is one of the alternate rich resources of bergenin and could be used as a therapeutic agent for diabetic testicular complications.

Keywords

Coral berry Trihydroxybenzoic acid glycoside Structure identification Assay validation Hyperglycemia-induced testis dysfunction Sperm quality 

Abbreviations

B100, B200, and B400

Diabetic rats treated with 100, 200, and 400 mg/kg of bergenin isolated from Ardisia colorata methanol leaf extract, respectively

AC

Ardisia colorata

ALT

Alanine aminotransferase

AO+

Abnormal DNA fluoresce, yellow or red

AO−

Normal DNA fluoresce, green

AST

Aspartate aminotransferase

C

Healthy untreated normal control (0.5% carboxy methyl cellulose)

CMC

Carboxy methyl cellulose

CPCSEA

Committee for the Purpose of Control and Supervision of Experiments on Animals

DC

Diabetic control (streptozotocin, 60 mg/kg)

DCA

Detrended correspondence analysis

DEPT

Distortedness enhancement by polarization transfer

DFI

DNA fragmentation index

DM

Diabetes mellitus

DSP

Daily sperm production

DSPr

Daily sperm production relative to testis weight

EMA

European Medicine Agency

FDA

Food and Drug Agency

FPG

Fasting plasma glucose

GC

Diabetic rats treated with glibenclamide (0.1 mg/kg)

GST

Glutathione S-transferase

HPLC

High-performance liquid chromatography

JTBS

Johnsen’s testicular biopsy score

LC

Liquid chromatography grade

LC-ESI-MS/MS

Liquid chromatography and electrospray ionization mass spectrometry

LOD

Limit of detection

LOQ

Limit of quantification

MANOVA

Multivariate analysis of variance

MDA

Malondialdehyde equivalents

MEACL

Methanol extract of Ardisia colorata leaf

MRM

Multiple-reaction monitoring

MSTD

Mean seminiferous tubule diameter

MZUAEC

Mizoram University Animal Ethical Committee

OECD

Organization for Economic Co-operation and Development

PCA

Principal component analysis

PCNA

Proliferating cell nuclear antigen

QC

Quality control

ROS

Reactive oxygen species

RSD

Relative standard deviation

SD

Standard deviation

SOD

Superoxide dismutase

STZ

Streptozotocin

TDI

Tubule differentiation index

TLC

Thin layer chromatography

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Notes

Acknowledgements

The authors acknowledge the instrumentation facility in Mizoram University funded by Department of Biotechnology, Government of India, New Delhi - Bioinformatics Infrastructure Facility (No. BT/BI/12/060/2012(NERBIF-MUA) and State Biotech Hub Programme (No. BT/04/NE/2009).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11356_2019_4139_MOESM1_ESM.pdf (1.7 mb)
ESM 1 (PDF 1726 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sanasam Sanjeev
    • 1
  • Meesala Krishna Murthy
    • 1
  • Maibam Sunita Devi
    • 1
  • Maurya Khushboo
    • 1
  • Zothanmawii Renthlei
    • 1
  • Kalibulla Syed Ibrahim
    • 2
  • Nachimuthu Senthil Kumar
    • 2
  • Vikas Kumar Roy
    • 1
  • Guruswami Gurusubramanian
    • 1
    Email author
  1. 1.Department of ZoologyMizoram Central UniversityAizawlIndia
  2. 2.Department of BiotechnologyMizoram Central UniversityAizawlIndia

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