Onions, a readily available culinary staple, have garnered increased scientific attention for their diverse array of health-promoting phytonutrients (Akash et al., 2014). Specifically, studies have demonstrated the potential of various onion components to positively impact glycemic control, oxidative stress, and cardiovascular health. For instance, oral administration of onion extract has been shown to modulate blood glucose levels in diabetic models (Akash et al., 2014), suggesting its potential as a dietary intervention for glycemic management. Additionally, topical application of onion oil has exhibited antioxidant activity against nicotine-induced oxidative damage in rats (Helen et al., 2000), hinting at its potential value in mitigating oxidative stress. Onion husk extracts have also emerged as promising functional ingredients, with research highlighting their diverse health benefits. Notably, studies have reported cholesterol-lowering effects mediated by onion peel extracts (Helen et al., 2000), along with antiproliferative activity against melanoma cells attributed to methanol extracts of onion husks (Arung et al., 2011). Furthermore, investigations by Gharibe et al. (2008) revealed the antispasmodic and antihypertensive properties of onion husks, further expanding their therapeutic potential. Collectively, these findings underscore the remarkable health-promoting properties of onions, warranting further comprehensive research to elucidate the mechanisms of action and translate these benefits into effective therapeutic strategies.
Onion skin emerges as a potential reservoir of bioactive compounds with significant antioxidant, anti-inflammatory, and antimicrobial properties (Singh et al., 2016; Manach et al., 2005). Tannins, constituting 45.12% of the identified bioactives, are well-established for their role in chronic disease prevention, particularly against cancer and cardiovascular ailments (Singh et al., 2016). Flanking them are flavonoids, at 18.13 mg/kg, another class of polyphenols lauded for their antioxidant, anti-inflammatory, and anticancer effects, potentially contributing to neuroprotection and cardiovascular health (Harborne & Williams, 2000; Middleton et al., 2000). While alkaloids and cardiac glycosides appear in lower concentrations (12.35 mg/kg and 3.37% respectively), their presence warrants further investigation due to their intriguing therapeutic potential and potential safety concerns (Klöckner et al., 2018). Collectively, these diverse bioactive compounds suggest onion skin holds immense promise as a readily available source of natural health-promoting agents. However, unlocking its full therapeutic potential and establishing safe utilization dosages require further comprehensive research.
Fourier-transform infrared (FT-IR) spectroscopic analysis of onion skin extract reveals a complex repertoire of functional groups indicative of a plethora of organic compounds (Silverstein & Webster, 2014; Stuart, 2018). The prominent peak at 3254.0 cm-1 signifies the abundance of hydroxyl (O-H) groups commonly found in alcohols, phenols, and carboxylic acids (Coates, 2006). A characteristic peak at 2120.9 cm-1 suggests the presence of alkynes or nitriles, potentially contributing to the extract's bioactivity (Smith, 2011; Barth, 2007). Aromatic and non-aromatic C = C bonds are evidenced by a peak at 1602.8 cm-1 (Smith, 2011; Pavia et al., 2015), while nitro compounds or aromatic C = C bonds further manifest at 1509.6 cm-1 (Larkin, 2011; Colthup et al., 1990). The peak at 1446.2 cm-1 confirms the presence of alkanes, alkenes, or alkynes (Smith, 2011; Bellamy, 1958). Amines, renowned for their diverse biological roles, are identified by the 1379.1 cm-1 peak (Nyquist, 1996; Nakamoto, 1986). Peaks at 1252.4 cm-1 and 1200.2 cm-1 indicate the presence of alcohols, esters, ethers, and aromatic C-O bonds, respectively (Smith, 2011; Lin-Vien et al., 1991). The peak at 1166.7 cm-1 confirms carbon-carbon bonds, and polysaccharides, crucial for plant cell structure and function, are identified by the peak at 1036.2 cm-1 (Movasaghi et al., 2008; Coates, 2000). These findings collectively suggest that onion skin extract harbours a rich tapestry of bioactive compounds, potentially offering a myriad of health benefits. However, further investigation is necessary to elucidate the specific molecular composition and biological activities of these constituents.
Gas chromatography-mass spectrometry (GC-MS) analysis of the flavonoid-rich fraction (FRF) extracted from onion husks revealed a promising array of 17 bioactive compounds (Cho et al., 2023). Five-methyl-2-phenylindolizine, constituting nearly half of the FRF, emerged as the most abundant compound (Cho et al., 2023). Methadone N-oxide, 3-phenylamine, S-oxide, and benzene, 1,1'-(1,2-cyclobutanediyl)bis-, trans- were identified as other major contributors (Cho et al., 2023). While the specific effects of these compounds require further investigation, some, like n-hexadecanoic acid and 5-eicosene, have shown potential antioxidant activity (Iqbal & Bhanger, 2006; Kubo et al., 1994). Additionally, 3-phenylthiane, S-oxide has demonstrated anti-inflammatory properties in preclinical studies (Chen et al., 2010), and methadone N-oxide exhibits potential antimicrobial activity against specific bacteria (Sheagren et al., 1977). Notably, compounds like 5-methyl-2-phenylindolizine and (1-ethylbuta-1,3-dienyl)benzene have shown interactions with the nervous system, warranting further investigation into their specific effects (Li et al., 2007; Yagi et al., 2001). In conclusion, the diverse spectrum of potentially bioactive compounds present in the onion husk FRF underscores its potential as a source of beneficial natural products. Future research is crucial to unlock its full potential for health and wellness applications (Cho et al., 2023).
The FRF of onion husk extract demonstrated excellent safety profiles in both single-dose and 14-day repeated-dose toxicity studies in rats. No significant changes were observed in body weight, organ weights (liver, kidney, heart), or hematological parameters, suggesting minimal impact on metabolism, energy balance, and overall health. The absence of organ damage in vital organs like the liver and kidneys further reinforces the low toxicity and potential safety of the FRF for consumption. These findings align with previous research on the non-toxic nature of onion husks and their extracts (Lee et al., 2021; Piechowiak & Balawejder, 2019), and pave the way for further exploration of the FRF's potential as a dietary supplement or functional food ingredient (Sharma et al., 2020).
While no adverse effects were observed at the tested doses (300 mg/kg and 2000 mg/kg) in the single-dose and 14-day repeated-dose studies, some minor fluctuations in blood parameters warrant further investigation. Increased band neutrophils in the FRF-treated groups may indicate early inflammation or stress response (Layton et al., 2023), necessitating further exploration of inflammatory markers. Elevated MCV and platelet fluctuations across groups also require additional monitoring to clarify potential influences on cell volume and bone marrow function, respectively (Aslinia et al., 2006). Notably, all other hematological parameters, including renal function markers (urea and creatinine), remained within normal ranges, implying minimal impact on major organ systems.
Histopathological assessments of the liver, kidney, and heart revealed no abnormalities in any of the FRF-treated groups, further corroborating the lack of organ damage and supporting the extract's safety profile. These findings are consistent with the positive safety profile reported for Allium cepa peels by Builders et al. (2023) and the potential antioxidant effects observed in the liver and brain of rats by Chernukha et al. (2021).
Overall, the present study provides compelling evidence for the low toxicity and potential safety of the FRF of onion husk extract for oral consumption. However, future investigations with larger sample sizes and longer treatment durations are crucial to confirm the long-term safety and potentially identify any delayed-onset adverse effects (Berlin et al., 2008). Additionally, exploring the mechanisms of action and effects on other organ systems and physiological processes will further elucidate the full therapeutic potential of this promising natural extract.
Mounting evidence suggests that therapeutic strategies for bipolar disorder (BD) target various pathways involving enzyme modulation, ion channels, G-protein coupled receptors, and intracellular mechanisms related to synaptic plasticity and neuroprotection (Gould et al., 2002). This study explores the potential of the flavonoid-rich fraction (FRF) of onion husk extract in preventing BD progression using a ketamine-induced hyperlocomotion model in rats. Ketamine, an NMDA receptor antagonist, mimics manic-like behavior in rodents, replicating some key features of BD episodes (Ni et al., 2022).
Our findings demonstrate that FRF pretreatment significantly attenuates ketamine-induced hyperactivity in the open field test, mirroring the effect of the established mood stabilizer lithium chloride (Debom et al., 2016). This suggests potential utility of FRF in managing manic episodes associated with BD. Mechanistically, FRF appears to counteract ketamine's effects by mitigating oxidative stress markers like elevated TBARS and ROS levels in the cerebral cortex and hippocampus (de Oliveira et al., 2009).
Additionally, FRF treatment reduces acetylcholinesterase (AChE) activity in these brain regions, indicating modulation of the cholinergic system (Haam and Yakel, 2017). The observed antioxidant properties of FRF are attributed to the presence of n-hexadecanoic acid and 5-eicosene, known for their potent antioxidant activity exceeding α-tocopherol and catechin (Iqbal & Bhanger, 2006; Kubo et al., 1994). These findings align with previous studies demonstrating the efficacy of plant extracts rich in phenolic compounds in mitigating ketamine-induced hyperlocomotion (Debom et al., 2016; Gazal et al., 2015; Chaves et al., 2020).
While the ketamine model lacks perfect specificity for mania (Sharma et al., 2016), the observed effects of FRF in preventing hyperlocomotion, reducing oxidative stress, and modulating cholinergic activity provide compelling evidence for its potential as a therapeutic candidate for BD. Future research using larger sample sizes and diverse models is necessary to validate these findings and elucidate the exact mechanisms of action underlying FRF's neuroprotective effects.
This research opens promising avenues for exploring the potential of FRF as a natural, potentially less-invasive therapeutic option for BD management. Further investigation into FRF's efficacy and safety profile alongside its interaction with established BD medications is crucial before clinical translation.