Wound Healing Activity of the Flavonoid-Enriched Fraction of <i>Selaginella bryopteris</i> Linn. against Streptozocin-Induced Diabetes in Rats
Arti Gautam,
Vikas Kumar,
Lubna Azmi,
Ch. V. Rao,
Mohammed Moizuddin Khan,
Beenish Mukhtar,
Mehnaz Kamal,
Muhammad Arif,
Seema Mehdi,
Saud M. Alsanad,
Osama A. Al-Khamees,
Talha Jawaid,
Aftab Alam
Affiliations
Arti Gautam
Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences (SHUATS), Prayagraj 211007, Uttar Pradesh, India
Vikas Kumar
Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences (SHUATS), Prayagraj 211007, Uttar Pradesh, India
Lubna Azmi
Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Science, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
Ch. V. Rao
Pharmacology Division, National Botanical Research Institute (CSIR), Lucknow 226001, Uttar Pradesh, India
Mohammed Moizuddin Khan
Department of Basic Medical Sciences, College of Medicine, Dar Al Uloom University, Riyadh 13314, Saudi Arabia
Beenish Mukhtar
Department of Basic Medical Sciences, College of Medicine, Dar Al Uloom University, Riyadh 13314, Saudi Arabia
Mehnaz Kamal
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Muhammad Arif
Faculty of Pharmacy, Integral University, Kursi Road, Lucknow 226026, Uttar Pradesh, India
Seema Mehdi
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru 570004, Karnataka, India
Saud M. Alsanad
Department of Pharmacology, College of Medicine, Imam Mohammad ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
Osama A. Al-Khamees
Department of Pharmacology, College of Medicine, Imam Mohammad ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
Talha Jawaid
Department of Pharmacology, College of Medicine, Imam Mohammad ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
Aftab Alam
Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, AL-Kharj 11942, Saudi Arabia
Diabetes and its complications, such as delayed wound healing, are increasing at an alarming rate in India, putting an enormous strain on the country’s limited healthcare resources. Hence, the present study proposes to screen/identify the possible mechanisms and to study the effect of the flavonoid-enriched fraction of Selaginella bryopteris extract against human keratinocyte cell lines (HaCaT) and streptozocin (STZ)-induced diabetic wounds in a male Wistar rat model. Chemical profiling was performed by an MTT assay. The obtained GC–MS analysis results showed the presence of amentoflavone, gallic acid, imidazole, palmitic acid, catechine, L-fucitol, lupeol, and myo-inositol as the major bioactive phytoconstituents. S. bryopteris induces the generation of ROS, the condensation of chromatin in the nucleus, and changes in the membrane potential of mitochondria in HaCaT cell lines. An S. bryopteris-dependent induction of apoptosis-mediated cell death in HaCaT cell lines was confirmed by an AO/PI analysis. Mitochondrial depolarization was reflected in JC-1 staining of cells. The wound size was reduced and epithelialization was enhanced. Keratinocyte migration decreased interleukins, TNF-α, IL-2, and IL-6 and the expression of pro-apoptotic (p53, caspase-3, caspase-9, and Bax) and anti-apoptotic (Bcl-2) genes in a dose-dependent manner. Keratinocyte migration increased antioxidant enzyme levels (CAT, SOD, MDA, and GSH). Wound healing is facilitated through the mitochondria-mediated apoptosis pathway, revealing a new area of diabetic wound therapy.
