Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

Table 1

Mechanism of action and side effects of some synthetic regimens used in the treatment of CVD, DM, and RA.

Number	Drugs; (brand names)	Mechanism	Side effects	Structure
Cardiovascular diseases
1	Aspirin; (Easprin®)	(i) Inhibiting the production of TXA2 by inactivation of COX-1 and COX-2 enzymes	(i) Stomach bleeding; (ii) Risk of hemorrhagic stroke ↑; (iii) Gastric ulcers; (iv) Stomach upset; (v) Heartburn; (vi) Nausea; (vii) Epigastric distress; (viii) Dyspepsia; (ix) Thrombocytopenia; (x) Fibrinolytic activity ↑
2	Quinapril; (Accupril®)	(i) Inhibiting ACE which catalyzes the formation of angiotensin II (a strong vasoconstrictor)	(i) Dizziness; (ii) Lightheadedness; (iii) Tiredness; (iv) Dry cough; (v) Nausea; (vi) Vomiting; (vii) Blurred vision; (viii) Chest pain; (ix) Confusion; (x) Sweating
3	Digoxin; (Lanoxin®)	(i) Inhibiting the Na-K-ATPase membrane pump resulting in an increase in intracellular sodium	(i) Dizziness; (ii) Fainting; (iii) Fast pounding or irregular heartbeat or pulse; (iv) Slow heartbeat; (v) Nausea; (vi) Vomiting; (vii) Headache; (viii) Loss of appetite; (ix) Diarrhea
4	Amlodipine; (Norvasc®)	(i) Decreasing arterial smooth muscle contractility and vasoconstriction by inhibiting the influx of calcium ions through calcium channels	(i) Dizziness; (ii) Lightheadedness; (iii) Swelling ankles/feet; (iv) Flushing; (v) Fatigue; (vi) Palpitations; (vii) Edema; (viii) Tightness in the chest; (ix) Wheezing
5	Isosorbide dinitrate; (Dilatrate-SR®)	(i) It is converted into NO which activates the enzyme guanylate cyclase that stimulates the synthesis of cGMP which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells eventually resulting in vasodilation	(i) Headache; (ii) Dizziness; (iii) Lightheadedness; (iv) Nausea; (v) Flushing; (vi) Unusual bleeding; (vii) Bruising; (viii) Rapid heart rate; (ix) Difficulty with breathing
Diabetes mellitus
1	Metformin (Glucophage®)	(i) Activating AMPK to inhibit hepatic glucose production; (ii) Increasing AMPK activity in skeletal muscle for glucose uptake by GLUT4 deployment to the plasma membrane	(i) Lactic acidosis; (ii) Dyspepsia; (iii) Nausea; (iv) Diarrhea; (v) Vomiting; (vi) Weakness
2	Pioglitazone; (Actos®)	(i) Activating PPARγ receptors to modulate the insulin-sensitive genes transcription for the reduction of insulin resistance	(i) Weight gain; (ii) Risk of bladder cancer; (iii) Sore throat; (iv) Muscle pain; (v) Tooth problems; (vi) May cause heart failure; (vii) Fluid retention; (viii) Peripheral edema
3	Glibenclamide; (DiaBeta®)	(i) Binding and inhibiting the ATP-sensitive potassium channels SUR1 receptor on the pancreatic cell surface, which causes membrane depolarization and opens the calcium channels for insulin exocytosis	(i) Nausea; (ii) Vomiting; (iii) Diarrhea; (iv) Increased appetite; (v) Heartburn; (vi) Stomach fullness; (vii) Weight gain; (viii) Hypoglycemia
4	Acarbose; (Precose®)	(i) Reversibly binding to pancreatic α-amylase and intestinal α-glucoside hydrolases to inhibit the hydrolysis of complex carbohydrates to glucose	(i) Diarrhea; (ii) Gas; (iii) Upset stomach; (iv) Constipation; (v) Stomach pain; (vi) Nausea; (vii) Loss of appetite; (viii) Jaundice
5	Human insulin; (Humulin R®)	(i) Binding to the IR and stimulating the downstream signaling molecules which regulates the GLU4 and PKC activity	(i) Pain; (ii) Mild itching; (iii) Redness; (iv) Swelling at the injection site; (v) Mild weight gain; (vi) Hypoglycemia
Rheumatoid arthritis
1	Methotrexate; (Trexall®)	(i) Inhibiting dihydrofolate reductase which is involved in purine metabolism; (ii) Inhibiting T-cell activation; (iii) Selectively downregulating B cells; (iv) Inhibiting methyltransferase activity, which leads to deactivation of immune system enzyme activities	(i) Nausea; (ii) Bloody vomiting; (iii) Stomach pain; (iv) Drowsiness; (v) Dizziness; (vi) Black, tarry stools; (vii) Sores in the mouth or lips; (viii) Blurred vision; (ix) Confusion; (x) Convulsions
2	Hydroxychloroquine; (Quineprox®)	(i) Inhibiting stimulation of the TLR-9; (ii) Inhibiting the production of rheumatoid factor	(i) Nausea; (ii) Stomach cramps; (iii) Loss of appetite; (iv) Diarrhea; (v) Dizziness; (vi) Headache; (vii) Convulsions; (viii) Weakness; (ix) Sore throat; (x) Fever; (xi) Unusual bleeding; (xii) Bruising
3	Sulfasalazine (Azulfidine®)	(i) Inhibiting NF-κB and exerting anti-inflammatory and/or immunomodulatory activities	(i) Stomach upset; (ii) Nausea; (iii) Vomiting; (iv) Loss of appetite; (v) Headache; (vi) Dizziness; (vii) Unusual tiredness; (viii) Fever; (ix) Sore throat; (x) Skin rash or itching; (xi) Bleeding gums; (xii) Dark urine
4	Leflunomide; (Arava®)	(i) Inhibiting mitochondrial enzyme dihydroorotate dehydrogenase and thus inhibiting the reproduction of rapidly dividing cells, especially autoimmune lymphocytes	(i) Diarrhea; (ii) Nausea; (iii) Dizziness; (iv) Skin rash; (v) Alopecia; (vi) AST ↑; (vii) ALT ↑; (viii) Bloody or cloudy urine; (ix) Cough; (x) Headache; (xi) Vomiting; (xii) Sore throat
5	Certolizumab; (Cimzia®)	(i) Binding and neutralizing the activity of TNFα; (ii) Inhibiting the release of IL-1β from monocytes	(i) Fever; (ii) Cough; (iii) Sore throat; (iv) Runny nose; (v) Frequent urination with burning sensation; (vi) Joint pain; (vii) Body aches; (viii) Headache; (ix) Loss of voice; (x) Ear congestion

AMPK: AMP-activated protein kinase; GLUT4: glucose transporter 4; SUR1: sulfonylurea receptor 1; IR: insulin receptor, PKC: protein kinase C; PPARγ: peroxisome proliferator-activated receptor gamma; ATP: adenosine triphosphate; TXA2: thromboxane A2; COX: cyclooxygenase: AST: aspartate aminotransferase; ALT: alanine aminotransferase; ACE: angiotensin converting enzyme; NO: nitric oxide; cGMP: cyclic guanosine 3′,5′-monophosphate.