Anti-aging potentials of a polyphenol-rich supplement from African Sorghum bicolor leaf sheaths: A narrative review

Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 58 REVIEW article Anti-aging potentials of a polyphenol-rich supplement from African Sorghum bicolor leaf sheaths: A narrative review Paul A. Adeleke 1 , Olajuwon Okubena 1, 2 , Abimbola Okubena 1, 2 , Abayomi M. Ajayi 1 Ololade Okubena 1, 2 , Favour B. Jegede 1 , and Solomon Umukoro 1 * 1 Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria 2 Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Afe Babalola University, Ekiti, Nigeria Article number: 231, Received: 02-11-2025, Accepted: 25-11-2025, Published online: 00-11-2025 HOW TO CITE THIS Adeleke et al. Anti-aging potentials of a polyphenol-rich supplement from African Sorghum bicolor leaf sheaths: A narrative review. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. [Article number: 231]. https://doi.org/10.5281/zenodo.17742769 Keywords: Age-related disease, anti-inflammatory, antioxidant, neuroprotection, Sorghum bicolor supplement Abstract: Aging is a complex biological process marked by a gradual decline in physiological functions and systemic deterioration, resulting in increased susceptibility to age-related diseases. There is increasing interest in the use of plant-based constituents in mitigating oxidative stress and inflammation, the major drivers of aging and age-related diseases. Polyphenol-rich plant-based constituents including Sorghum bicolor supplement (SBS) with potent antioxidant, anti-inflammatory and neuroprotective properties, have demonstrated anti-aging potential. The aim of this review is to provide documentation from published literature on the anti-aging potentials of SBS that may elicit the need for its clinical evaluation for age-related diseases. A literature search was conducted using PubMed electronic database with subject headings, related to the mechanisms of aging, age-related diseases, health burden of aging population, and polyphenols for a healthy life span. It also included the source, bioactive constituents, and antiaging potential of SBS. The findings obtained from the review showed that SBS mitigated age-related diseases in various animal models. The supplement extended the life span of Drosophila melanogaster and improved their motor functions. The SBS inhibited the activity of collagenase and elastase enzymes involved in premature skin aging and exhibited cytoprotection against hyposaline-induced red blood cells hemolysis. The anti-aging potential of SBS relates to its potent antioxidant, anti-inflammatory, immune-modulating, and neuroprotective properties. These findings provide a strong foundation for further preclinical and clinical studies to validate the therapeutic potentials of SBS in promoting a healthier lifespan and enhancing the quality of life of the aging population. Introduction Aging is a complex, irreversible, and inevitable biological process marked by a gradual decline of physiological functions and systemic deterioration, resulting in increased susceptibility to age-related diseases [1]. Oxidative stress and inflammation are key drivers of aging, contributing to telomere attrition, DNA damage, mitochondrial dysfunction, genetic instability, immune impairment, and metabolic disorders [2, 3]. Aging increases the incidence and severity of the debilitating nature of age-related diseases such as cerebrovascular disorders, neurodegenerative diseases, diabetes, visual impairment, musculoskeletal disorders, and cancer [4, 5]. Thus, when Copyright© 2025. This open-access article is distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 59 aging reaches a certain critical threshold, organ and tissue functions rapidly deteriorate, increasing the incidence and mortality of age-related diseases. However, the decrease in physical strength and cognitive impairments, particularly dementia, are the prominent features of the aging process. Interestingly, aging and chronic diseases are highly associated with increased oxidative stress, elevated chronic low-grade inflammation and increased DNA damage [6, 7]. Although the prospect of increased lifespan is desirable, there is a need to consider the challenges of disability and the burden of living with age-related diseases. Notably, the qualities of life of most elderly people are grossly impaired instead of a healthy life span [8]. Globally, the proportion of older people (aged 60 years and above) is rising, and it has been estimated that it will nearly double by 2050 [9]. Developing nations are undergoing rapid demographic transitions, with the rise of aging populations [10]. The increase in the global aging population, age-related diseases the focus of attention worldwide for several reasons. For example, the functional decline in the elderly poses serious challenges, arising from the increased burden of age-related diseases and the shortening of healthy life span. Aging comes with financial pressure in terms of loss of economic productivity and medical expenses [1, 11]. Therefore, it is highly imperative to search for effective interventions that can positively prolong the healthy lifespan of the aging population. The current focus of aging research has shifted towards interventions targeting oxidative stress and inflammation to promote not just longevity but a healthier lifespan [1, 11]. Phytochemicals have shown promising efficacies in addressing the multifaceted pathways associated with aging [1, 12, 13]. The polyphenol-rich SBS derived from the leaf sheaths of the African Sorghum bicolor variety has demonstrated antioxidant, antiinflammatory, immune modulating, and neuroprotective properties in various experimental models [14-16]. In addition, these bioactive constituents can mitigate aging-related diseases and promote healthy living among the elderly. Nevertheless, available experimental data on SBS have yet to be extensively reviewed to highlight its anti-aging potential for a healthy long life-span. Consequently, this review underscores its anti-aging properties, based on information from the PubMed electronic database. The findings obtained from the review can provide a strong foundation for further preclinical and clinical studies to validate the therapeutic potential of SBS in promoting a healthier lifespan and quality of life of the aging population. Literature search strategy: This review analyzed information obtained from a comprehensive search of literature using the PubMed electronic database with the subject headings, relating to mechanisms of aging, age-related diseases, health burden of aging population, and polyphenols for a healthy life span. The search includes the source, bioactive constituents, and antiaging potential of SBS. We excluded studies with non-availability of the full-text articles, personal opinions and those not written in the English language. Discussion of key findings: The published articles retrieved based on the literature search, were discussed, mainly on four broad categories, including health care burden for the elderly, biological basis of aging, polyphenols for aging and antiaging properties of SBS. The antiaging properties of SBS were further discussed under four broad subtopics. Health care burden for the elderly: Globally, the proportion of older people, 60 years and above, is on the increase and it has been estimated that it will double by 2050 [9]. However, the aging population has several consequences on economies, social services and healthcare systems, and they are often associated with differing levels of disability and a deteriorating quality of life. The functional decline in the elderly poses serious challenges as well as financial pressures in terms of reduced productivity and cost of medical expenses [5, 17]. Financial and economic factors significantly affect health outcomes and well-being for elderly people. Specifically, studies have shown that disease burdens can lead to a decrease in economic growth and increased families’ health-related Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 60 expenditure [5, 18, 19]. In fact, the burden of diseases among the elderly people could increase families’ caregiving liability, affecting resource allocation and labor employment within the household [18, 19]. The need for caregiving can affect household income and resources, particularly for families caring for elderly relatives with disabilities. The impacts of the aging population on health systems have been documented in the literature. For example, it has been reported that in the United States, people aged 65 and above, accounted for 30% of healthcare expenditure in 2008, a figure expected to rise to 50% by the year 2030 [5, 20]. In Sub-Saharan Africa, the effects of aging would even be more devastating in countries like Nigeria, Ghana, Kenya, and Uganda, because of the projected increase in the number of older adults [21]. Taken together, these observations suggest the need to develop therapeutic strategies that can enhance the quality of life of the aging population. Biological basis of aging: The remarkable influence of aging on the genesis of chronic diseases in humans and their progression highlights the need to understand the basic mechanisms that underlie the aging process and human longevity. Understanding the key molecular and cellular processes that are involved in aging may promote the development of therapeutic agents that could delay senescence and improve overall human health [22]. Although the dilemma behind why we age, and the causes of aging appear unfathomable, a plethora of theories have been propounded over the years to unravel the complex nature of the aging process [23]. These include telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide (NAD+) levels, impaired autophagy, stem cell exhaustion, inflammation, loss of protein balance, oxidative stress, deregulated nutrient-sensing, altered intercellular communication and dysbiosis [1, 22, 24]. The deregulation of these interconnected pathways leads the cells to a state of senescence, which contributes to aging and the genesis of age-related diseases (Figure 1). Indeed, many of these interrelated mechanisms, especially DNA damage, have been touted as drivers of aging [24]. Figure 1: Key documented molecular basis of aging and age-related diseases Telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macroautophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis are some of the key processes that underlie aging [1]. Aging leads to organ/systemic deterioration and an increase in susceptibility to age-related diseases such as cardiovascular, cerebrovascular, degenerative joint disease, diabetes, Parkinson’s disease, Alzheimer’s disease and cancer [1]. Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 61 DNA damage is the major internal factor that triggers genomic instability, epigenetic changes, protein stress, impaired mitochondrial function, and telomere dysfunction [1, 25]. Notably, the continuous accumulation of DNA-damaged cells triggers cell death and senescence, eventually leading to chronic inflammation, loss of function, atrophy, and aging of cells and tissues [26]. Nevertheless, the unanswered question about what factor triggers DNA damage, ab initio, suggests that identifying, which of the inter-related mechanisms are drivers or passengers of aging remains a big challenge [24]. However, the free radical or oxidative theory appears to be the most popular theory of aging, with several studies demonstrating the injurious nature of excessive reactive oxygen species (ROS) and oxidative stress via mechanisms, relating to the shortening of telomeres, mitochondrial dysfunction, and the initiation of aging-related inflammatory responses [27]. The theory also has a lot of evidencebased support [28]. Proposed by Harman in 1956, the free radical theory holds that aging is associated with the accumulation of ROS that exert oxidative damage to cellular biomolecules, especially the DNA (Figure 2), ultimately leading to a decline in physiological function and death [29]. The cellular degeneration and early apoptosis caused by free radicals produce oxidative stress, regarded as the main pathological culprit in premature aging [29]. Moreover, oxidative stress is further aggravated by a variety of stressors, which may accelerate aging and age-related diseases, as well as increased vulnerability to death [30]. Figure 2: Role of free radicals in oxidative stress and the aging process [3] The free radical theory holds that aging is associated with the accumulation of ROS that exert oxidative damage to cellular biomolecules, especially the DNA, ultimately leading to a decline in physiological function and causing cellular death [29]. The cellular degeneration and early apoptosis caused by free radicals produce oxidative stress, which is regarded as the main pathological culprit in premature aging [27, 29] Indeed, oxidative stress and inflammation underlie the telomere attrition, DNA damage, mitochondrial dysfunction, genetic instability, impaired immune functions and metabolic deregulations (Figures 3-5) that underpin the aging process [1]. The accumulation of ROS that exerts oxidative damage to cellular biomolecules and apoptosis might be the primary initiator of the complex interconnected pathways that lead to deterioration in bodily function with aging. As shown in Figures 4 and 5, ROS induces telomere damage, leading to its shortening and decapitation, which further supports the central role of oxidative stress in the aging process. ROS and deregulated metabolites (NAD+) contribute to mitochondrial dysfunction, and the development of several agerelated diseases [1]. Studies have shown that increased ROS levels contribute to decreased replication of stem cells [31]. In addition, senescent cells secrete pro-inflammatory cytokines, and studies have shown that ROS and inflammation are all important inducers of cell senescence [32]. Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 62 Figure 3: Drivers of DNA damage and the resulting systemic consequences of loss of cellular functions and the genesis of age-related diseases [1] The sources of various injurious substances that cause genetic abnormalities, dysfunctional telomeres, epigenetic alterations, and mitochondrial dysfunction have been established in the literature [1, 3]. Ultimately, DNA damage leads to cellular dysregulations and promotes the development of age-related diseases [1] Figure 4: The role of ROS in telomere decapitation and accelerated cell senescence [1] ROS have been implicated in telomere decapitation and accelerated cell senescence [1]. Accumulated senescent cells are known to secrete a complex set of pro-inflammatory cytokines, the senescence-associated secretory phenotype (SASP), which enhances T cells and macrophages, resulting in systemic chronic inflammation and inflammation-related diseases [1]. Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 63 Figure 5: Drivers of mitochondrial dysfunction and development of several age-related diseases [1] Healthy mitochondrial metabolic function is a key factor in ensuring long-term health during the aging process and is susceptible to various environmental factors and endogenous metabolites. Alterations in mitochondrial function have widespread adverse effects on intracellular homeostasis and lead to systemic organ decline and the development of several age-related diseases through complex signaling mechanisms [1] In terms of aging, exposure to sources of damage over the human lifespan varies among individuals and may partly explain why people age differently [33]. However, the free radical theory has recently faced severe criticisms [34] including failure in addressing some critical aspects of aging. This realization has led some authors to suggest that the free radical theory of aging needs to be modified and improved upon. It likewise echoes the notion that no single theory has been able to explain the mechanism of aging [34] and none is generally considered as the gold standard [35]. Although the extant theories on aging often compete and conflict with one another, a maximally correct theory may trigger significant breakthroughs in the discovery of antiaging interventions. This may come via the integration of some existing theories for a better understanding of the mechanisms of aging and development of antiaging therapy [34]. Nevertheless, the free radical theory of aging is still one of the most promising theories of aging and constitutes the primary target for antiaging research. An imbalance between free radical generation and antioxidative capacity causes oxidative damage to DNA, proteins, and mitochondria during the aging process. Interestingly, Auley et al. [36] had further highlighted the significant role of oxidative stress in the network theory of aging, as interactions between the different key mechanisms relating to defective mitochondria, oxidative stress, DNA damage, and dysregulation of cellular signaling (Figure 6). Additionally, antioxidant supplementation has been shown to retard the aging process and delay the onset of age-related diseases, as well as extend human health and longevity [3]. Owing to these packets of scientific knowledge, current antiaging research is primarily focused on the use of antioxidant polyphenolic compounds to promote not only longevity, but a healthier lifespan [3]. Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 64 Figure 6: Complex patterns of interactions between oxidative stress, DNA, protein damage, mitochondrial dysfunction and dysregulation of cellular signaling in aging process [36] The dysregulation of these interconnected pathways makes the cells senescent, contributing to aging and the genesis of age-related diseases [24]. The accumulation of ROS that exerts oxidative damage to cellular biomolecules and apoptosis might be the primary initiator of the complex interconnected pathways that lead to deterioration in bodily function during aging. Polyphenolic plant-based preparations for aging The desire to slow down the aging process and extend healthy life span has been the vigorous pursuit of the scientific field in recent times. The advocacy for lifestyle changes, including calorie restriction, sleep regulation, and exercise, has been reported to be insufficient in extending the healthy lifespan of older people or preventing age-related diseases [1]. Thus, many studies have focused on the mechanisms underlying the aging process and exploring ways of targeting the hallmark features of aging, particularly oxidative stress and inflammation. Polyphenolic-rich phytochemicals have shown promising antiaging properties by targeting the multifaceted pathways associated with aging. They exhibit numerous biological activities; including antioxidant effects, free radical scavenging, anti-inflammatory properties, neuroprotection, and immunomodulation pharmacological targets for antiaging studies [37, 38]. Polyphenolic compounds, found abundantly in plant-based foods, are increasingly being recognized for their potential anti-aging properties. Polyphenols are essential components of human diets, and epidemiological data indicate that consuming foods rich in antioxidants lowers the incidence of oxidative stress-related aging disorders such as diabetes, cardiovascular diseases, neurodegenerative diseases and cancer [12, 13]. These compounds can help combat cellular damage, improve various physiological functions, and potentially slow down the aging process. Indeed, polyphenols protect cells from oxidative stress, delay cellular aging, and safeguard tissues from degradation [38]. Certain polyphenols can reduce inflammation, a key driver of age-related conditions, by suppressing inflammatory signaling pathways. In addition, polyphenolic compounds are generally regarded as safe and effective in preventing age-related diseases [38, 39]. Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 65 Dietary polyphenolic components can extend the lifespan of various model species by removing senescent cells, maintaining mitochondrial homeostasis, suppressing inflammatory response, and countering oxidative stress [12, 13]. In fact, increasing evidence has demonstrated that dietary polyphenol intake can delay aging and age-related diseases [38]. The antiaging potential of these phytoconstituents is related to their anti-inflammatory and antioxidant capabilities and promotion of cellular repair [12, 40]. Also, polyphenols can regulate immune function and improve resistance to diseases by inhibiting the NF-κB pathway and pro-inflammatory gene expression, suppressing the enzymes related to the production of ROS, and up-regulating other endogenous antioxidant enzymes [41]. Polyphenols have shown protective effects on cognitive functions, alleviating neurodegenerative diseases by preventing cellular damage, and enhancing DNA repair machinery [42]. Epidemiological studies show that adhering to the Mediterranean dietary pattern, which is a plant-based diet, was associated with better health outcomes during aging [43]. These findings further suggest that diets rich in polyphenol-based food plants positively influence the hallmark of aging-related disease risks and longevity [43]. Remarkably, diets rich in vegetables and fruits with antioxidant and anti-inflammatory activities are linked to a low incidence of age-related diseases [44, 45]. Based on these findings, it is logical to think that the nutrients and bioactive molecules found in plant-based foods play a key role in acting synergistically to positively influence the different pathways of the aging processes. Antiaging properties of the SBS supplement Sorghum bicolor (L. Moench, family Poaceae), popularly known as millet, sweet Sorghum, or guinea corn, is widely cultivated in many tropical countries of the world for its economic, nutritional, and medicinal values [14]. Sorghum bicolor is a unique plant-derived food and ranked fifth after wheat, maize, rice, and barley in the world’s cereal production [46]. Besides being used as a staple food by the natives of Africa, Central America and South Asia, the sorghum grain is used worldwide as animal feed [47]. In ethnomedicine, different parts of the plant, including the grain, are used for a myriad of chronic diseases [14, 47]. However, the leaf-sheaths portion of the plant have been recognized for the presence of high contents of polyphenolic bioactive compounds (Table 1). These bioactive compounds have exhibited potent antioxidant, anti-inflammatory, immunomodulating and neuroprotective, and chemopreventive properties [14, 16, 48], suggesting the potential roles of SBS in mitigating age-related diseases and as a possible elixir to healthy aging. In this review, we present evidence from the literature alluding to the antiaging potential of SBS and its capacity to promote healthy aging. Therapeutic potential of SBS supplement in aging-related diseases The antiaging potential of SBS is implied in its reported mitigation of age-related diseases such as stroke, arthritis, cancer, movement disorders, and memory deficits [14]. It is worth noting that ischemic stroke is the second leading global cause of death and physical disabilities among the elderly. It is due to the activation of oxidative and inflammatory pathways triggered by the obstruction of cerebral blood flow and subsequent neuronal cell death [49]. Thus, targeting oxidative and inflammatory pathways with bioactive constituents of plant origins offers promising therapeutic strategies for ischemic stroke [49-51]. Epidemiological data have revealed that regular consumption of plant-based foods rich in polyphenols can reduce the risk of stroke [51]. Lending credence to this, preclinical studies showed that SBS reduces the neurological deficits in a global ischemic stroke model through inhibition of oxidative stress, pro-inflammatory cytokines (IL-6 and TNF-α) and NF-kB reactivity in rats [52]. It protected the neurons of the striatum, prefrontal cortex, and hippocampus, as well as increasing the population of viable neuronal cells in these brain regions of ischemic rats [52]. The potential benefits of SBS in Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 66 neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD) have also been investigated in scopolamine-induced amnesia and rotenone-induced motor dysfunctions, respectively, [53, 54]. The findings showed that the supplement attenuated amnesia and motor dysfunctions by augmenting the neuronal antioxidant protective mechanisms. It reduced pro-inflammatory cytokines in rotenone-induced Parkinsonian-like motor dysfunctions in rats [54], indicating its therapeutic potential in movement-related disorders associated with aging. Rheumatoid arthritis is another age-related disease in the elderly. It is a chronic inflammatory autoimmune disease due to progressive inflammation of the synovial tissues, and cartilage destruction in the affected joints [55, 56]. The joints’ health-promoting effects of SBS was demonstrated when it was tested in rats subjected to intraarticular injection of complete Freund's adjuvant (CFA). The supplement was shown to have reduced pain sensitivity in the hyperalgesia test and joint inflammation in rats with intra-articular injection of CFA. The supplement also positively modulated oxidative stress, pro-inflammatory cytokines, apoptotic factors (caspase 3 and caspase 9), NF-κB, myeloperoxidase, and nuclear factor erythroid 2-related factor 2 (Nrf2), and articular tissue degeneration in the ankles of CFA-arthritic rats [57]. Notably, these biomarkers and transcription factors (NF-κB and Nrf2) play pivotal roles in cellular aging and age-related pathologies, including arthritis [58-59]. Thus, the findings that SBS positively modulated these biochemical pathways and transcription factors further substantiate its anti-aging potential in promoting healthy joints in the elderly. Studies have shown that SBS is rich in diverse bioactive polyphenol-rich constituents (Table 1) such as luteolin, narigenin, apigenindin, apigenin and luteolinidin [16, 60], most of which exert diverse pharmacological activities; including anti-inflammatory, antimutagenic, anticancer, immunomodulatory, antioxidant, and neuroprotective effects [16, 61, 62]. SBS is rich in minerals such as iron, zinc, calcium, copper, magnesium, selenium, phosphorus, sodium and potassium, and omega-6 fatty acid [14], which are essential for metabolism and neuronal functioning [63]. Omega-3 and -6 fatty acids, for example, have demonstrable anti-inflammation, anti-apoptosis and neuroprotective properties [64, 65]. Table 1: Phytochemical constituents of leaf sheaths of Sorghum bicolor, Jobelyn® [60] Mediterranean Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2789-1895 online www.medjpps.com ISSN: 2958-3101 print Adeleke et al. Mediterr J Pharm Pharm Sci. 2025; 5(4): 58-77. 73 14. 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Author declarations: The authors confirm that they have followed all relevant ethical guidelines and obtained any necessary IRB and/or ethics committee approvals. Generative AI disclosure: No Generative AI was used in the preparation of this manuscript.