The Hypotensive Activity of Royal Jelly

Royal Jelly (RJ), a nutrient-rich secretion produced by bees, has long been recognized for its diverse physiological regulatory functions, including vasodilation and blood pressure-lowering effects. Early studies documented these vascular and hypotensive properties (Albert S, et al., 1999; Schmitzova J, et al., 1998). Recent research, both in vitro and in vivo, suggests this effect likely results from the synergistic action of multiple components, such as unsaturated fatty acids, proteolytic peptides, acetylcholine-like substances, and bioactive factors modulating the NO/cGMP signaling pathway.

1. ACE Inhibitory Activity of Unsaturated Fatty Acids

An in vitro study by Okuda et al. (1998) first indicated that unsaturated fatty acids in RJ, namely trans-2-octenoic acid and 10-hydroxydecenoic acid (10-HDA), could inhibit Angiotensin-Converting Enzyme (ACE) activity. However, their inhibitory potency was relatively weak; for instance, 10-HDA at concentrations above 1 mmol·L⁻¹ achieved less than 50% ACE inhibition. Furthermore, the susceptibility of these fatty acids to enzymatic degradation in the gastrointestinal tract has cast doubt on their ability to maintain effective in vivo concentrations for blood pressure control. Thus, while contributing, unsaturated fatty acids are likely not the primary active hypotensive components in RJ.

2. ACE Inhibitory Activity of MRJP1 Hydrolysates

Research focus has shifted towards the Major Royal Jelly Proteins (MRJPs), particularly MRJP1 (approx. 57 kDa, forming a hexamer of ~350 kDa). Matsui et al. (2002) demonstrated that while native MRJP1 itself shows no significant ACE inhibition, it can be hydrolyzed by digestive enzymes in the gastrointestinal tract to produce low-molecular-weight peptides with potent ACE inhibitory activity. In spontaneously hypertensive rats (SHR), these peptides significantly lowered diastolic blood pressure by an average of (22.7 ± 3.6) mmHg (P < 0.05), identifying them as a crucial source of RJ's in vivo hypotensive effect.

The structural integrity of MRJP1 is vital for bioactivity. Kamakura et al. (2001) reported that MRJP1 undergoes specific degradation during prolonged or warm storage, while other RJ components remain stable, establishing MRJP1 as a key biochemical marker for RJ freshness. The same study found that fresh RJ (ED₅₀ = 100 μg·mL⁻¹) significantly promoted DNA synthesis and proliferation in rat primary hepatocytes, an activity lost after storage at 40°C for 7 days due to MRJP1 degradation, further underscoring its role in RJ's bioactivity.

3. In Vivo Hypotensive Effects: NO/cGMP Pathway and Calcium Channel Modulation

Pan Y et al. (2019) systematically investigated RJ's hypotensive mechanism in SHRs. Rats were divided into WKY control, SHR control, and SHR-RJ groups, with the latter receiving 1 g/kg/day RJ orally for 4 weeks. Results showed:

Significant reduction in systolic (SBP) and diastolic (DBP) blood pressure in the SHR-RJ group.

• Marked increase in plasma nitric oxide (NO) levels.
• Pronounced endothelium-dependent vasodilation in isolated aortic rings.
• Significant inhibition by RJ of norepinephrine (NE)-induced intracellular Ca²⁺ release and high potassium-induced extracellular Ca²⁺ influx.
• Significant increase in cGMP levels.

These findings indicate that RJ induces vasodilation and lowers blood pressure by enhancing NO production, elevating cGMP levels, and modulating calcium channels. Additionally, acetylcholine-like substances in RJ with muscarinic receptor agonist activity may further promote vasodilation by activating NO synthesis.

4. Physiological Regulatory Role of Vitamin B6, Inositol, Acetylcholine, and Other Components

RJ is rich in active substances like vitamin B6, inositol, and acetylcholine, which are believed to enhance vascular elasticity, improve hemorheology, and promote oxygen supply, thereby assisting in maintaining normal blood pressure (Sun Haidong et al., 2003). These components likely play a synergistic role in RJ's overall hypotensive effect, particularly in promoting vasodilation and potentially preventing atherosclerosis.

In summary, the hypotensive function of Royal Jelly appears to be achieved through multiple integrated mechanisms:

• Weak ACE inhibition by unsaturated fatty acids.Ge
• neration of ACE-inhibitory peptides from the gastrointestinal hydrolysis of MRJP1.
• Activation of the NO/cGMP pathway by acetylcholine-like substances.
• Vasodilation induced by calcium channel inhibition.
• Auxiliary regulation of vascular function by components like vitamin B6 and inositol.

Among these, MRJP1-derived peptides and the NO/cGMP signaling pathway are likely central to RJ's blood pressure-lowering activity. Future research involving clinical trials, structural analysis of active peptides, and studies on metabolic stability is essential to further elucidate RJ's hypotensive mechanisms and advance its application in functional foods and supportive therapies.

References

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