Table 2.

Clinical conditions and possible mechanism of yohimbine action.

Disorders	Mechanism of action/clinical effect	References
Erectile disorder	Control ejaculatory reflex in a rat model by antagonizing AR-α2	[57]
	Dose-dependent relaxant effect in rat corpus cavernosum	[58]
	Improve blood flow and boost erectile function in combination with L-arginine	[59]
	Prolong effect of sildenafil on the erectile process in rat model	[12]
	Maintain a balance between the non-adrenergic, non-cholinergic nerves nitric oxide stimulus, and counterbalance the sympathetic noradrenergic nerves	[60]
	Effective ingredient of testosterone and erectile disorder supplement	[65]
	Synergistic effect of increased penile artery inflow with arginine	[66]
Myocardial dysfunction	LPS-induced TNF-α production via α2A-AR	[70]
	Inhibits inflammatory responses and improves septic in rats via α2A-AR blockage	[74]
	Reversal of LPS-induced decline in left ventricular ejection fraction, stroke volume, cardiac output, along with an increase in left ventricular end-systolic volume	[68]
	Decrease septic cardiomyopathy via α2A-AR blockage and increases cardiac norepinephrine concentration, and inhibit cardiac endothelial activation	[69]
	Inhibit myocardial apoptosis and I-κBα phosphorylation. Reverses LPS-induced decrease in left ventricular ejection and fractional shortening, lowering of TNF-α, caspase 3/7, and IL-1β in the heart tissue. Results cardiac presynaptic α2A-AR inhibition via iNOS expression and TNF-α production in combination with berberine	[76]
	Inhibition of collagen-epinephrine interactive platelet aggregation	[80]
	Effectively inhibit adrenaline potentiated platelet aggregation via α2-AR blocking	[81]
	Inhibit α2B-AR aggregation in platelets and prevents atherothrombotic events	[82]
	Co-block 5-HT2A and α2-AR receptors on platelets and suppresses ADP mediated platelet aggregation	[9]
Anti-inflammatory	Suppresses the NF-κB pathway, reduces IL-1β or noradrenaline induce IL-6 upregulation, ameliorate cartilage destruction in condylar processes and upregulate tyrosine hydroxylase	[11]
	Inhibit pro-inflammatory cytokines and modulate antioxidant states, reduces expression of COX-2, TNF-α, and NF-ĸB, ESR, WBC, and CRP in rats	[88]
	Protect renal ischemia/reperfusion-induced acute kidney injury through blockage of α2-adrenoceptor in rats	[88]
	Reno-protective effect on LPS-induced acute kidney injury in rats and suppresses cytokine mRNA, iNOS, and block NF-κB nuclear localization. Enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) promoting IL-10 expression	[89]
	Immunomodulate and inhibit the JNK, ERK, NF-κB and other pathways via upregulation of IL-10 in mice	[90]
	Inhibit TNF-α, IL-1β, and IL-6 overproduction relieving the severity of pulmonary inflammation induced by endotoxin blockage of α2A AR. Also improve oxygenation index, white blood cell count, and lung histopathological scores in rats	[91]
Anticancer	Antagonistic activities against GPCR-mediated cancer	[10]
	Modulate steroid 5α-reductase pathway against benign prostatic hyperplasia by downregulating steroid 5α-reductase type 2 and reduced levels of dihydrotestosterone, prostatic acid phosphatase, prostate-specific antigen, proliferating cell nuclear antigen, and steroid 5α-reductase	[103]
	Cytotoxic with a β-carbolinium group on human MCF-7 breast, SWS80 colon, and A549 lung cancer cell lines with IC50 values of 25.5, 22.6, and 26.0 μM, respectively	[105]
	Induces apoptosis in pancreatic (PC-2 and PC-3) cancer cell lines	[104]
	Cytotoxic against human pancreatic cancer cells (PATU-8988), human gastric cancer cells (SGC-7901), and normal human gastric mucosal cells (GES-1)	[1]
Polycystic ovary syndrome (PCOS)	Reduces PCOS parameters viz. bodyweight, LH, insulin in reproductively mature female rabbits	[106]
	Reduces LH concentration and normalization of ovulatory cycles by increasing the concentration of oestrogen in PCOS rats	[108]
Rescue therapy in acute pesticide ingestion	Regained consciousness, weaned off mechanical ventilation after accidental ingestion of amitraz without any side effects and could serve as an antidote for faster neurological recovery, prevent bradycardia, and provide hemodynamic stability in severe amitraz poisoning	[109]