Therapeutic Potential of Neolamarckia cadamba and Terminalia arjuna: A Review on Anti-inflammatory and Wound Healing Applications in Diabetic Patients

Diabetes mellitus is frequently complicated by chronic non-healing wounds, especially diabetic foot ulcers. These lesions are difficult to resolve because diabetic tissue typically exhibits persistent inflammation, delayed macrophage resolution, excessive reactive oxygen species, reduced fibroblast migration, poor collagen deposition, impaired angiogenesis, and high infection risk [6][7]. In this context, phytomedicines are attractive because they often act on several stages of wound repair simultaneously rather than targeting a single pathway. Normal wound healing proceeds through hemostasis, inflammation, proliferation, and remodeling, but diabetes disrupts the orderly transition between these stages, causing wounds to remain trapped in a chronic inflammatory state. Elevated cytokine signaling, oxidative damage, and microbial colonization prevent the development of healthy granulation tissue and delay re-epithelialization. As a result, diabetic wounds often become recurrent, slow to close, and resistant to standard therapy. Because diabetic wound pathology involves multiple interrelated mechanisms, single-target drugs are often insufficient. This has led to increasing interest in phytotherapeutic approaches, which may simultaneously exert anti-inflammatory, antioxidant, antimicrobial, and regenerative effects. Natural products are particularly attractive for wound care because they can influence several stages of the repair process at once, thereby addressing the complex microenvironment of diabetic ulcers more comprehensively than conventional monotherapies. Within this context, Neolamarckia cadamba and Terminalia arjuna are two medicinal trees with significant traditional and pharmacological value. N. cadamba has been reported to suppress pro-inflammatory mediators such as TNF-α, IL-1β, and COX-2, while its fruit extracts also show antioxidant and antibacterial activity linked to phenolic constituents including quercetin and caffeic acid derivatives. These properties make it especially relevant for controlling the inflammatory and oxidative phases that dominate early diabetic wound pathology.

T. arjuna, in contrast, has stronger direct experimental evidence for wound healing. Bark fractions rich in tannins, flavonoids, and triterpenoids have been shown to improve epithelialization, tensile strength, granulation tissue formation, and antimicrobial defense in wound models. Its anti-inflammatory and antioxidant effects further support its usefulness in chronic wounds where persistent inflammation and tissue instability delay recovery. From a therapeutic perspective, these two plants may have complementary roles in diabetic wound management. N. cadamba may be more useful in the early phase by reducing inflammatory signaling and limiting oxidative injury, whereas T. arjuna may contribute more strongly to proliferative and remodeling phases by supporting collagen maturation, wound contraction, and structural repair. This complementary potential is particularly relevant in diabetic patients, whose wounds require coordinated control of inflammation, infection, redox imbalance, and matrix regeneration. Therefore, the present review focuses on the anti-inflammatory and wound-healing potential of Neolamarckia cadamba and Terminalia arjuna in diabetic patients. By synthesizing their phytochemical profiles, pharmacological actions, and mechanistic relevance to diabetic wound repair, this review aims to highlight their promise as topical adjuncts in future wound management strategies. Neolamarckia cadamba and Terminalia arjuna are longstanding medicinal trees in South Asian traditional medicine. Their relevance to diabetic wound care lies in the convergence of anti-inflammatory, antioxidant, antimicrobial, and tissue-regenerative effects [1][5]. The present review evaluates their therapeutic potential in diabetic patients, with emphasis on pathways linked to inflammation control and wound closure.

2. Pathophysiology of Diabetic Wound Impairment

A diabetic wound typically remains trapped in the inflammatory phase. Elevated TNF-α and other pro-inflammatory cytokines contribute to cellular dysfunction, while oxidative stress damages lipids, proteins, and DNA. At the tissue level, keratinocyte and fibroblast migration is reduced, macrophage polarization is disturbed, and vascularization is insufficient [6]. These defects collectively lower collagen synthesis and slow epithelial recovery. Effective interventions should therefore reduce inflammation, restore redox balance, support angiogenesis, and promote matrix rebuilding [7].

Figure 1: Pathological Mechanisms of Impaired Diabetic Wound Healing

3. Neolamarckia cadamba: Botanical and Pharmacological Profile

3.1 Phytochemical basis

Studies on N. cadamba have identified bioactive monoterpenoid indole alkaloids in addition to broader phytochemical classes such as phenolics and flavonoid-related constituents [1]. Fruit extracts also contain appreciable phenolics, including caffeic acid, tannic acid, syringic acid, and quercetin, which are associated with antioxidant and antibacterial effects [2].

3.2 Anti-inflammatory activity

Experimental evidence shows that extracts and fractions of N. cadamba significantly reduce carrageenan-induced paw edema and acetic acid-induced writhing. In macrophage-based assays, isolated constituents suppressed inflammatory mediators including TNF-α, IL-1β, and COX-2 [1]. These findings support the claim that N. cadamba can modulate the inflammatory phase of wound healing.

3.3 Relevance to wound repair

Although direct diabetic wound studies on N. cadamba are still limited, its anti-inflammatory and antibacterial properties are highly relevant to ulcer healing. A plant that reduces inflammatory mediator release while limiting bacterial proliferation may help shift chronic wounds toward granulation and epithelialization. Its phytochemical profile suggests potential for topical use in diabetic wound formulations [2][1].

4. Terminalia arjuna: Botanical and Pharmacological Profile

4.1 Phytochemical basis

T. arjuna bark is rich in tannins, flavonoids, triterpenoids, glycosides, phenolic acids, and saponins [5][8]. This composition is highly relevant to tissue repair because tannins can exert astringent, antimicrobial, and protein-binding effects, while flavonoids and triterpenoids contribute antioxidant and anti-inflammatory actions.

4.2 Anti-inflammatory activity

Multiple studies support the anti-inflammatory potential of T. arjuna. Both hydroalcoholic extract and Arjuna Ksheera Paka showed significant inhibition of carrageenan-induced paw edema in mice [3]. These findings are consistent with broader reviews describing T. arjuna as an anti-inflammatory and antioxidant medicinal plant [5].

4.3 Wound healing activity

The strongest direct wound-healing evidence among the two plants is available for T. arjuna. Fractionation studies showed that topical application of bark-derived phytoconstituents significantly improved incision wound tensile strength and excision wound epithelialization in rats. Fraction I, which consisted mainly of tannins, was particularly effective and also demonstrated antimicrobial activity against several bacterial pathogens [4]. This is highly relevant for diabetic ulcers, where bacterial burden and poor tissue strength are common barriers to healing.

figure: 2 Comparative pharmacological profile of neolamarckia cadamba & terminalia arjuna in wound healing

Table 1. Major phytochemicals

5. Mechanistic Rationale for Diabetic Wound Healing

Both plants likely promote diabetic wound repair through overlapping mechanisms:

5.1 Suppression of chronic inflammation

Diabetic wounds are characterized by persistent TNF-α-driven inflammation. N. cadamba suppresses TNF-α, IL-1β, and COX-2 in experimental models, while T. arjuna has repeatedly demonstrated anti-inflammatory activity in vivo [1][3].

5.2 Antioxidant defense

Oxidative stress is a key obstacle to repair. N. cadamba fruit extracts exhibit strong DPPH and ABTS scavenging activity, and T. arjuna has demonstrated marked antioxidative effects in several experimental systems [2][9]. This antioxidant capacity may protect fibroblasts, endothelial cells, and keratinocytes in wound tissue.

5.3 Collagen deposition and matrix repair

Tannin-rich T. arjuna fractions enhanced tensile strength and epithelialization, with associated increases in granulation tissue parameters [4]. These effects suggest improved collagen organization and extracellular matrix maturation.

5.4 Antimicrobial support

Secondary infection is a major cause of delayed diabetic wound closure. T. arjuna fraction I displayed antimicrobial activity against important wound pathogens, while N. cadamba fruit extracts also demonstrated antibacterial mechanisms [4][2].

5.5 Potential vascular and regenerative support

Successful wound healing requires angiogenesis and tissue remodeling. In diabetic models more broadly, improved VEGF expression, collagen deposition, and epithelial recovery are associated with enhanced wound closure [10] [11]. These endpoints are relevant for evaluating future N. cadamba and T. arjuna formulations.

Table 2. Proposed mechanisms in diabetic wound healing

figure 3: mechanistic pathway of herbal extract initiated wound healing in diabetic ulcers