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Pharmacology and Mechanisms of Natural Medicine in Treatment of Type 2 Diabetes Mellitus

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Evidence Based Validation of Traditional Medicines

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder that is affecting the worldwide population with high rates of morbidity and mortality. The most prevalent case of DM is type 2 diabetes mellitus (T2DM) which is characterized by insulin resistance and insulin secretion defect due to impaired β-cell functioning. Epidemiological studies implied that the number of diabetic cases has been doubled during the past two decades and has turned out to be a global epidemic accompanied by severe metabolic and endocrine complications over time. The rising emergence of T2DM in children, adolescents, and young adults signifies it to be one of the most dominant perturbing features of its kind. Proper diet control, moderate exercise, and hypoglycemic and lipid-lowering agents are some evident strategies that have been employed in the management of T2DM so far. However, a distinct possibility of severe diabetic complications still exists despite the therapeutic benefits achieved by these drugs. Various in vitro and in vivo models have suggested that phytochemicals exert several pharmacological effects on metabolic disorders such as in hyperglycemia, hypertension, and hyperlipidemia by modulating oxidative stress, inflammatory response, autophagy, and anti-apoptosis effects. Additionally, they have positive modulatory actions on molecular targets of T2DM like insulin signaling, IRS, glucose transporters, α-glucosidase, PPARγ, DPP-IV, PTP1B, NF-κB, etc. Regulation of these maladaptive pathophysiological mechanisms can improve insulin-resistant state, lower blood glucose levels, and protect against various macrovascular and microvascular complications. Thus, natural products have garnered significant interest as bioactive agents in the management of T2DM. This chapter aims to overview the activities and underlying mechanisms of natural medicine in the management of T2DM.

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Abbreviations

AGE:

Advanced glycation end products

AGT II:

Angiotensin II

Akt:

Also known as protein kinase B (PKB)

AMPK:

Adenosine monophosphate-activated protein kinase

Bcl-2:

β-cell lymphoma protein 2

BMP 4:

Bone morphogenic protein 4

cAMP:

Cyclic AMP

CB1:

Cannabinoid receptor type 1

CCL 5:

Chemokine ligand 5

CCR 5:

Chemokine receptor type 5

CTGF:

CCN2 or connective tissue growth factor

DM:

Diabetes mellitus

DPP:

Dipeptidyl peptidase

eNOS:

Endothelial nitric oxide synthase

ERK:

Extracellular signal-regulated kinases

FFA:

Free fatty acids

Foxp3:

Forkhead box

G6PD:

Glucose-6-phosphate dehydrogenase

GIP:

Gastric inhibitory polypeptide

GLP:

Glucagon-like peptide

GLUT:

Glucose transporter

GSK 3:

Glycogen synthase kinase

HbA1C:

Glycosylated hemoglobin

HDL:

High-density lipoproteins

Hep G2:

Human hepatocyte carcinoma cell line

HFD:

High-fat diet

HGP:

Hepatic glucose production

HMG-coA:

3-Hydroxy-3-methyl-glutaryl-Coa reductase

ICAM:

Intercellular adhesion molecule

IDF:

International Diabetes Federation

IKK:

IκB kinase

IL-6:

Interleukin 6

IRS-1:

Insulin receptor substrate-1

JAK:

Janus kinase

JNK-c:

Jun N-terminal kinases

LDH:

Lactate dehydrogenase

LDL:

Low-density lipoproteins

MAPK:

Mitogen-activated protein kinases

MCP-1:

Monocyte chemoattractant protein-1

MMP:

Matrix metalloproteinase

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NLRP:

Nod-like receptor protein

NO:

Nitric oxide

Nrf2:

Nuclear factor erythroid 2-related factor 2

PCSK9:

Pro-protein convertase subtilisin-kexin type 9

PI3K:

Phosphoinositide 3-kinases

PKC:

Protein kinase C

PPAR:

Peroxisome proliferated-activated receptor

PTP-IB:

Protein tyrosine phosphatase 1B

RAAS:

Renin angiotensin aldosterone system

RAGE:

Receptor for advanced glycation end products

ROS:

Reactive oxygen species

S1P:

Sphingosine-1-phosphate

SIRT1-NAD:

dependent protein deacetylase sirtuin-1

SphK1:

Sphingosine kinase 1

SREBP:

Sterol regulatory element binding proteins

STAT:

Signal transducers and activators of transcription

STZ:

Streptozotocin

T2DM:

Type 2 diabetes mellitus

TBARS:

Thiobarbituric acid-reactive substances

TG:

Triglycerides

TGF:

Tumor growth factor

TNF-α:

Tumor necrosis factor-α

VEGF:

Vascular endothelial growth factor

VLDL:

Very-low-density lipoprotein

α-SMA:

Alpha-smooth muscle actin

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  1. Dr. B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur, India

    Tanushree Karmakar, Rituparna Chaki & Nilanjan Ghosh

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  2. Rituparna Chaki
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  1. Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India

    Subhash C. Mandal

  2. NEF College of Pharmacy, Guwahati, Assam, India

    Raja Chakraborty

  3. Faculty of Pharmaceutical Science, Assam down town University, Guwahati, Assam, India

    Saikat Sen

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Karmakar, T., Chaki, R., Ghosh, N. (2021). Pharmacology and Mechanisms of Natural Medicine in Treatment of Type 2 Diabetes Mellitus. In: Mandal, S.C., Chakraborty, R., Sen, S. (eds) Evidence Based Validation of Traditional Medicines. Springer, Singapore. https://doi.org/10.1007/978-981-15-8127-4_49

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