Baicalin protects against heat-induced multiorgan dysfunction via organ-specific protein modulation - integrative in silico and in vivo evidence

Q: What medical problem does the study address?

It addresses heatstroke-induced multiorgan dysfunction syndrome, a life-threatening emergency involving oxidative stress, inflammation, and metabolic failure across major organs.

Q: Which proteins were identified as therapeutic targets for baicalin?

Hsp70, Hsp27, AQP1, IL-6R, and CYP3A4 were identified as key heat-responsive proteins involved in heat-induced stress and organ injury.

Q: How was baicalin evaluated in vivo?

Baicalin was tested in a rat whole-body hyperthermia model (42 ± 0.5 °C for 4 h), where it reduced histopathological lesion severity and altered protein expression patterns.

Sep 29, 2026

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Heatstroke-induced multiorgan dysfunction is a life-threatening emergency driven by systemic oxidative stress, inflammation, and metabolic collapse across vital organs. The study evaluates baicalin, a naturally occurring flavone glycoside, as a multitarget cytoprotective agent against systemic hyperthermia using integrated computational and experimental approaches. Five heat-responsive proteins were targeted, supported by docking, MD simulations, PCA/FEL, DFT, and in vivo validation in a rat whole-body hyperthermia model.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

Introduction

Heatstroke and systemic hyperthermia as clinical emergencies

Baicalin as a cytoprotective natural polyphenol

Mechanistic rationale and study objective

RSC Advances PAPER Cite this: RSC Adv., 2026, 16, 1264 Received 29th July 2025 Accepted 14th November 2025 DOI: 10.1039/d5ra05510e[rsc.li/rsc-advances](rsc.li/rsc-advances) Baicalin protects against heat-induced multiorgan dysfunction via organ-speciﬁc protein modulation: integrative in silico and in vivo evidence Anjali Kumari,†a Aisha Tufail, †b Magda H. Abdellattif, c Amit Dubey *d and Rakesh Kumar Sinha*a Heatstroke-induced multiorgan dysfunction represents a life-threatening clinical emergency characterized by systemic oxidative stress, inﬂammation, and metabolic collapse across vital organs. Despite advances in supportive care, there remains a critical lack of multitarget pharmacological interventions that address the underlying molecular pathology. Here, we evaluated baicalin, a naturally occurring ﬂavone glycoside, for its multiorgan protective eﬃcacy against systemic hyperthermia through an integrated computationalexperimental framework. Five key heat-responsive proteins—heat shock protein 70 (Hsp70), heat shock protein 27 (Hsp27), aquaporin-1 (AQP1), interleukin-6 receptor (IL-6R), and cytochrome P450 3A4 (CYP3A4)—were identiﬁed as therapeutic targets based on their roles in heat-induced stress and organ injury. Molecular docking revealed strong binding aﬃnities (DG = −9 .3 to −8 .5 kcal mol−1), supported by molecular dynamics (MD) simulations (2000 ns) showing conformational stability (root mean square deviation, RMSD < 0.25 nm; 5–8 hydrogen bonds) and favorable molecular mechanics–generalized born surface area (MM-GBSA) binding energies (up to −65 .3 kcal mol−1 for Hsp70-baicalin) . Principal component analysis (PCA) and free energy landscape (FEL) mapping conﬁrmed thermodynamic stability, while density functional theory (DFT) calculations (highest occupied molecular orbital-lowest unoccupied molecular orbital, HOMO–LUMO gap = 3.45 eV) supported baicalin's electronic reactivity. In vivo validation using a rat whole-body hyperthermia model (42 ± 0.5 °C for 4 h) demonstrated signiﬁcant attenuation of heat-induced pathology. Histopathological scoring revealed reduced lesion severity in the brain, heart, kidneys, liver, and lungs following baicalin pre-treatment (50 mg kg−1, intraperitoneal) . Western blot and densitometric analyses conﬁrmed downregulation of Hsp70, Hsp27, and IL-6R alongside restoration of CYP3A4 (p < 0 .05) . Complementary absorption, distribution, metabolism, excretion, and toxicity (ADMET) and ProTox-II analyses predicted a high safety margin (LD50 z 5000 mg kg−1; non-hepatotoxic; nonmutagenic) . Collectively, these ﬁndings establish baicalin as a promising multitarget natural cytoprotective agent and underscore the translational potential of combining computational pharmacology with in vivo disease modeling to accelerate cytoprotective drug discovery. 1. Introduction Heatstroke and systemic hyperthermia are critical medical emergencies that can rapidly progress into life-threatening multiorgan dysfunction syndrome (MODS) . Sustained core body temperatures exceeding 40 °C disrupt cellular aDepartment of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India. E-mail: [rakishsinha@bitmesra.ac.in](rakishsinha@bitmesra.ac.in)[ ](rakishsinha@bitmesra.ac.in)bComputational Chemistry and Drug Discovery Division, Quanta Calculus, Greater Noida-201310, Uttar Pradesh, India cChemistry Department, College of Sciences, University College of Taraba, Taif University, Taif, Saudi Arabia dCenterfor Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. E-mail: [amitdubey@saveetha.com](amitdubey@saveetha.com); [ameetbioinfo@gmail.com](ameetbioinfo@gmail.com) † First equal authorship. homeostasis and initiate a complex network of pathophysiological cascades—including excessive generation of reactive oxygen species, mitochondrial impairment, proin􀀁

FAQs

What medical problem does the study address?

It addresses heatstroke-induced multiorgan dysfunction syndrome, a life-threatening emergency involving oxidative stress, inflammation, and metabolic failure across major organs.

Which proteins were identified as therapeutic targets for baicalin?

Hsp70, Hsp27, AQP1, IL-6R, and CYP3A4 were identified as key heat-responsive proteins involved in heat-induced stress and organ injury.

How was baicalin evaluated in vivo?

Baicalin was tested in a rat whole-body hyperthermia model (42 ± 0.5 °C for 4 h), where it reduced histopathological lesion severity and altered protein expression patterns.

Sep 29, 2026

Uploaded by Angel