Acknowledging the use of botanicals to treat diabetic foot ulcer during the 21st century: A systematic review

Table 1 Clinical cases assessing the role of medicinal plants in the treatment of diabetic foot ulcer

Scientific name	Family	Sanskrit name	Country	Parts used	Sample size	Other ingredients	Mode of administration	Metabolites or nutraceuticals along with result	Duration	Inference of the study	Ref.
Actindia deliciosa	Actinidiaceae	Kiwi	Iran	Fruit	37	NR	Injection (3 mm thick layer) every 12 h	Actinidin and ascorbic acid/angiogenesis (increased), epithelialization, vascularization and granulation. Ulcer size (decreased)	11.24 ± 3.66 d (experimental), 17.76 ± 4.88 d (control)	Complete wound healing and effective	Mohajeri et al[35]
Actindia deliciosa	Actinidiaceae	Kiwi	Iran	Fruit	18	Eucerin cream	Topical (wound was covered with the mixture) every 24 h	Actinidin, wound size (decreased) (0.94 ± 0.58 cm2), experimental vs control (% change in wound size: -1.25 ± 0.21 vs 0.21 ± 0.05)	28 d	Reduction in wound size and effective	Kardoust et al[36]
Ageratina pichinchensis	Asteraceae	-	Mexico	Aerial part	36	Cold cream	Topical one a week	7-O-(β-D-glucopyranosyl)-galactin/wound size (decreased)	65.47 ± 47.08 d experimental); 77.46 ± 50.80 d (control)	Complete wound healing and effective	Romero-Cerecero et al[37]
Calendula officinalis	Asteraceae	Zergul	Brazil	Flowers	32	NR	Topical (5 mL) once a day	Calendula oil/wound healing (increased), pain (decreased)	30 d	Reduction in wound size and effective	Carvalho et al[73]
Calendula officinalis	Asteraceae	Zergul	Brazil	Flowers	84	NR	Spray twice daily	Wound healing (increased), 78% had complete healing after 30 wk	15.5 ± 6.7 wk	Reduction in wound size and effective	Buzzi et al[74]
Garcinia kola	Clusiaceae	Balya	Nigeria	Seed	120	NR	Oral (capsule) 250-500 mg	Wound healing (increased), Reduction in wound size by 63.30% in experimental group	63-84 d	Reduction in wound size and effective	Bolajoko et al[24]
Kalanchoe pinnata	Crassulaceae	Pranabijah	West Indies	Leaves	478	NR	Plaster (boiled leaf) and poultice once to thrice daily	Wound healing (increased)	9 d	Effective	Cawich et al[99]
Linum usitatissimum	Linaceae	Atasi	Iran	Seed oil	60	NR	Supplement (1000 mg/d omega-3 fatty acid from flaxseed oil)	Omega-3- fatty acid/ulcer length (decreased), width and depth, experimental vs control % change in (ulcer length: -2.0 ± 2.3 vs -1.0 ± 1.1 cm; width: -1.8 ± 1.7 vs -1.0 ± 1.0 cm; and depth: -0.8 ± 0.6 vs -0.5 ± 0.5 cm)	84 d	Reduction in wound size and effective	Soleimani et al[25]
Melilotus officinalis	Fabaceae	Vanamethika	Iran	NR	10	NR	Intravenous infusion	Melilotus/wound (decreased) size (reduced by 50%), experimental vs control (wound size: 6.69 ± 60 vs 12.32 ± 11 cm2)	56 d	Reduction in wound size and effective	Bagheri et al[113]
Melilotus officinalis	Fabaceae	Vanamethika	Iran	NR	40	NR	Orally twice a day	Melilotus/wound healing (increased), experimental vs control (completely healed: 90.0% vs 70.0%)	84 d	Complete wound healing and effective	Bahrami et al[114]
Momordica charantia	Cucurbitaceae	Karavella	Indonesia	Leaf	30	NR	Oral (6 g) per day	Wound healing (increased), experimental vs control: [TNF-α serum levels (pg/mL): -29.50 ± 8.6 vs -202.47 ± 610.2; PEDIS degree (decreased): 1.9 ± 0.6 vs 2.2 ± 0.8]	28 d	Not effective	Rosyid et al[122]
Olea europaea	Oleaceae	Jaitun	Iran	Fruit	60	NR	Topically (oil) once a day	Wound healing (increased), experimental vs control (completely healed: 76.60% vs 0.00%)	28 d	Complete wound healing and effective	Abdoli et al[130]
Olea europaea	Oleaceae	Jaitun	Iran	Fruit	34	NR	Topical (oil) once a day	Wound healing (increased). Ulcer area (decreased) and depth, experimental vs control (completely healed: 73.33% vs 13.30%; change in ulcer (area: -54.7% ± 28.8% vs +2.7% ± 47.2%), depth (area: -60.1% ± 13.8% vs -29.6% ± 12.6%)	28 d	Complete wound healing and effective	Nasiri et al[131]
Plantago major	Plantaginaceae	Asvagola	Iran	Leaves	94	Gel	Topically (oil) once a day	Plantamajoside/wound healing (increased), experimental vs control (completely healed: 64.00% vs 20.50%)	14 d	Complete wound healing and effective	Ghanadian et al[125]
Plantago major and Aloe vera	Plantaginaceae, Asphodelaceae	Asvagola and Ghrit kumara	Iran	NR	40	NR	Intervention twice a day	Ulcer surface decreased, ulcer depth decreased	28 d	Reduction in wound size and effective	Najafian et al[55]
Plectranthus amboinicus and Centella asiatica	Lamiaceae and Apiaceae	Yavani, Mandukaparni	Taiwan	NR	24	Cream (composed of cetostearyl alcohol, ireine, liquid petrolatum, methyl paraben propyl paraben, Span 60, Tween 60, white petrolatum, water, and pigments)	Topically (2 mm thickness) twice a day	Wound healing (increased), experimental vs control [improved Wagner grade: 90.9% vs 70.0% (% change in wound size: -27.18 vs -22.64)]	14 d	Reduction in wound size and effective but not significant compared to controlled group	Kuo et al[84]
Quercus infectoria	Fagaceae	Mayakku	Thailand	Nutgalls	51	Ethanol	Topical once a day	Wound healing (increased), experimental vs control (80.7% vs 20.0%)	96 d	Complete wound healing and effective	Chokpaisarn et al[152]
Sesamum radiatum and Azadirachta indica	Pedaliaceae and Meliaceae	Tila, Nimba	India	Seed and leaves	15	Ghee and honey	Topically (3 mm thick) once a day	Wound size and exudates (decreased), no granulation, reduction in wound size by 88.0% in the experimental group	45 d	Complete wound healing and effective	Tripathy et al[160]
Teucrium polium	Lamiaceae	-	Iran	Aerial part	70	Eucerin	Topically twice daily	Wound healing (increased), experimental vs control; ulcer area (decreased): 0.717 ± 0.19 cm2vs 1.63 ± 0.72 cm2	28 d	Reduction in wound size and effective	Fallah Huseini et al[169]
Tinospora cordifolia	Menispermaceae	Guduchi	India	NR	50	NR	Intervention	Wound healing (increased), experimental vs control (change in ulcer area: 0.15 cm2/d vs 0.07 cm2/d; ulcer perimeter: 0.09 cm2/d vs 0.07 cm2/d; ulcer depth: 2.20 cm2/d vs 1.40 cm2/d; wound score: 14.40 cm2/d vs 10.60 cm2/d; no. of debridements: 1.90 cm2/d vs 2.50 cm2/d)	28 d	Reduction in wound size and effective	Purandare and Supe[176]
Vasconcellea cundinamarcensis	Caricaceae	-	Brazil	Latex	50	NR	Intervention thrice a week	Wound healing (increased), experimental vs control. Completely healed: 68.7% vs 31.3%)	112 d	Complete wound healing and effective	Tonaco et al[182]
Vernonia amygdalina	Asteraceae	-	Nigeria	Leaves	120	NR	Oral (capsule) 250-500 mg/kg body weight	Wound healing (increased), reduction in wound size by 60.0% in experimental group	63-84 d	Complete wound healing and effective	Bolajoko[26]

NR: Not reported; TNF-α: Tumour necrosis factor alpha.