Hrev_master Healthcare in Low-resource Settings 2024; volume 12:11835 The effectiveness of wound cleansing using Cocor Bebek (Kalanchoe pinnata) leaves in healing diabetic foot ulcers Imroatul Farida, Christina Yuliastuti, Nuh Huda, Nur Muji Astuti, Vedia Lutfiana Sekolah Tinggi Ilmu Kesehatan Hang Tuah Surabaya, Indonesia Abstract This study aimed to evaluate the effectiveness of Cocor Bebek (Kalanchoe pinnata) leaves in wound cleaning for diabetic foot ulcers (DFU) and compare it with the use of NaCl solution. Diabetes mellitus (DM) and its complications, such as DFU, pose a global health problem with increasing prevalence. Given the escalating occurrence of DFU, timely and effective treatment is crucial to prevent severe complications, including amputation. This research employed a quasi-experimental design with a pretest-posttest control group and was conducted at Rumah Luka Surabaya, Indonesia. The sample comprised 40 respondents with DFU, divided into an intervention group (using Cocor Bebek leaves) and a control group (using NaCl solution). Respondents’ characteristics, including age, sex, occupation, duration of dia- betes, and other factors, were assessed to understand their impact on the response to treatment. The results demonstrated a signifi- cant improvement in DFU wound healing in the intervention group after using Cocor Bebek leaves (p<0.05), along with reduced scores on Bates Jensen Wound Assessment Tool (BWAT) indicators such as wound edge, tunnel, and necrotic tissue type. Conversely, the control group using NaCl solution also exhibited significant improvement in wound healing (p<0.05), with decreased scores on indicators such as the amount of necrotic tis- sue and the quantity of exudate. This study underscores the poten- tial of Cocor Bebek leaves in aiding wound healing in DFU, evi- dent from clinical improvements and reduced BWAT scores. However, further research and clinical trials are needed to compre- hensively support these findings and understand the mechanism of action, as well as the safety of using Cocor Bebek leaves in diabet- ic patients. Introduction Diabetes Mellitus (DM) has emerged as a significant global health challenge, marked by an increasing prevalence rate.1 A con- sequential complication of diabetes is the occurrence of Diabetic Foot Ulcers (DFU), which has become a pressing global health concern, affecting regions such as Asia, ASEAN, and Indonesia.2 As the number of individuals diagnosed with diabetes continues to rise, the prevalence of diabetic foot ulcers is escalating, posing substantial health implications globally and regionally.3 Notably, 80% of cases with Diabetes Mellitus develop DFU complications, leading to leg amputation in severe instances.4,5 Approximately 14-24% of diabetic foot patients eventually require amputation, with 75% of individuals with diabetes experiencing foot problems.5–8 Among the diabetic population, 44% undergo relatively expensive and prolonged diabetic wound treatment, as highlighted by Perkeni.6 The mortality rate due to diabetic ulcers reaches 17- 23% post-amputation, with a one-year mortality rate of 14.8%, escalating to 37% three years after amputation.7 Diabetic foot ulcers exhibit a prolonged healing process compared to non-dia- betic wounds due to their chronic nature.9 Chronic wound condi- tions can result in persistent tissue damage and, ultimately, ampu- tation if infections are not treated properly.10,11 Wound cleansing, a crucial aspect of both acute and chronic Correspondence: Nuh Huda, Hang Tuah College of Health Sciences Surabaya, Surabaya, Indonesia. E-mail: nuhhuda@stikeshangtuah-sby.ac.id Key words: diabetes mellitus, diabetic foot ulcer, kalanchoe pinnata, non-communicable disease, wound cleansing. Contributions: IF, conceptualization, data curation, formal analysis, methodology, validation, visualization, writing – original draft, review & editing; CY, collecting data, conceptualization, data curation, formal analysis, methodology; NH, conceptualization, investigation, validation, and writing – original draft, review, editing, corresponding; NMA, con- ceptualization, formal analysis, validation, and, review & editing, VL, collecting data, writing – original draft. Conflict of interest: the authors declare no conflict of interest. Ethics approval and consent to participate: this study had received ethical approval from the health research Ethics Committee of Sekolah Tinggi Ilmu Kesehatan Hang Tuah Surabaya, Indonesia, with a certificates of ethical Eligibility variety: PE/44/VI/2022/KEPK/SHT dated June 15th, 2022. Patient consent for publication: the researcher did not include the respon- dent's name on the data collection sheet, simply providing a specific code or number on the sheet to maintain the confidentiality of the identity of research subjects to be published in this article. Funding: this research did not receive external funding. Availability of data and materials: all data generated or analyzed during this study are included in this published article. Acknowledgment: we specific our private appreciation and gratitude to Sekolah Tinggi Ilmu Kesehatan hang Tuah Surabaya for the very mean- ingful support. Thank you furthermore may to all research respondents and nurses at Rumah Luka Surabaya, Indonesia. Received: 18 September 2023. Accepted: 21 December 2023. Early access: 8 February 2024. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2024 Licensee PAGEPress, Italy Healthcare in Low-resource Settings 2024; 12:11835 doi:10.4081/hls.2024.11835 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organi- zations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. [page 216] [Healthcare in Low-resource Settings 2024;12:11835] Non -co mmerc ial us e o nly wound care, involves the use of cleaning fluids selected based on their effectiveness and lack of cytotoxicity.12,13 Despite a spectrum of treatment approaches for DFU, the negative consequences of inadequate or delayed intervention persist.14 Infections pose a sig- nificant risk, exacerbating wound conditions and potentially lead- ing to severe complications, including the necessity for amputa- tion.15 Consequently, the importance of effective and timely treat- ment cannot be overstated in preventing complications that jeopar- dize the limbs of individuals with diabetes.14,16 One alternative avenue for wound cleansing involves the use of Cocor Bebek Leaves (Kalanchoe pinnata) as a natural substi- tute. Although these leaves exhibit considerable potential as an herbal component for cleansing diabetes foot ulcers (DFU), their utilization remains limited. Despite being readily available and cost-effective for DFU sufferers, Cocor Bebek leaves (Kalanchoe pinnata) are not yet commonly employed in DFU wound cleaning procedures. Recognizing the need for more natural and effective treatment options for DFU, there is a growing interest in exploring the healing potential of Cocor Bebek Leaf (Kalanchoe pinnata)17. Nevertheless, the adoption of this leaf as a wound cleansing agent for DFU is progressing slowly, with many individuals still unaware of its benefits18. Wound cleansing using Cocor Bebek leaves presents a poten- tial solution for DFU healing19. These leaves contain active sub- stances, including steroid glycosides, saponin compounds, tannins, flavonoids, and terpenoids, offering cooling, antiseptic, astringent, anti-inflammatory, fever-reducing, asthma-relieving, stomach ulcer-treating, ulcer-healing, and wound-healing properties20. Previous research, including Kony Putriani’s study in 202321, demonstrates that Cocor Bebek (Kalanchoe pinnata) contains heal- ing compounds such as flavonoids, saponins, and tannins. Kony Putriani’s research also evaluates the antibacterial effectiveness of methanol extract against Propionibacterium acnes and Staphylococcus aureus.21 In white rats, a 20% concentration of Cocor Bebek leaf ethanol extract ointment proves most effective in healing incision wounds.22 Additional studies indicate anti-inflam- matory activity in rat feet induced by carrageenan with a 2% ethanol extract of Cocor Bebek leaves.21 Purwanitiningsih (2020)23 examines the antibacterial efficacy of Cocor Bebek leaf extract against Salmonella typhi using the Kirby Bauer method, revealing high antibacterial power. Another study indicates that higher con- centrations of Cocor Bebek leaf extract expedite the healing pro- cess of cut wounds in white rats, with a 15% concentration proving most effective.24 While existing research highlights the efficacy of Cocor Bebek in wound healing and antibacterial activity, it is essential to note that the focus has primarily been on these aspects rather than the plant’s application for diabetic diseases. This study aimed to eval- uate the effectiveness of Cocor Bebek (Kalanchoe pinnata) leaves in wound cleaning for diabetic foot ulcers (DFU) and compare it with the use of NaCl solution. Materials and Methods This study utilized a quasi-experimental design with a pretest- posttest control group approach. The research was conducted in June 2022 at a Health Facility in Surabaya, Indonesia. The sample for this study consisted of 40 respondents divided into two groups: the intervention group and the control group. Group selection was carried out using the Simple Random Sampling method. The inclu- sion criteria involved patients with diabetic foot injuries of degree 2-3, blood sugar levels < 200 mg/dL, regular intake of diabetes drugs or insulin injections, and having a normal weight (BMI = 18.5-22.9). The dependent variable in this study was wound cleaning using Cocor Bebek leaves (Kalanchoe pinnata), while the independent variable was wound healing in diabetic patients. Self-administered questionnaires were employed to collect sociodemographic data, including age, sex, occupation, duration of diabetes, history of dia- betes, history of diabetic foot wound care, history of diabetic diet, exercise habits, heredity, drug consumption, comorbidities, and blood sugar levels during data collection. The instrument used for wound cleaning with Cocor Bebek leaves (Kalanchoe Pinnata) was a Standard Operating Procedure for wound treatment involving a decoction of 5 pieces of Cocor Bebek leaves (100 gr) and 1 L of water, boiled for 15 minutes until the cooking water reduced to 500 ml for the intervention group, while the control group was treated with usual wound washing using NaCl solution 0.9%. An instrument to measure diabetic foot wound healing employed the Bates Jensen Wound Assessment Tool (BWAT) with 13 indicators, including size, depth, wound edge, tunnel, necrotic tissue type, necrotic tissue count, exudate type, exudate count, skin color around the wound, peripheral edema, hardening of peripheral tissue, granulation tissue, and epithelialization. DFU score mea- surements were performed over 14 days or 6 interventions. Data were analyzed using the Wilcoxon test within each group (intervention and control), and the Mann-Whitney test was utilized to assess the relationship between the two groups with a signifi- cance level of 5%. This research received approval from the Ethics Committee of Stikes Hang Tuah Surabaya with reference number PE/44/VI/2022/KEPK/SHT dated June 15, 2022. Results Based on Table 1, the intervention group was dominated by respondents aged 30-40 years, female gender, work as housewives, suffer from DM for less than 12 months, and have a family history of DM. The majority of respondents did not exercise regularly, took DM or insulin drugs regularly, maintained a diet, and had ran- dom blood sugar levels <200 mg / dL. Meanwhile, the control group was dominated by respondents aged 50-60 years, female gender with other types of work, suffering from DM for 1-2 years and 2-3 years, having a hereditary history of DM, not exercising regularly, taking DM drugs or insulin regularly, maintaining a diet, and having random blood sugar levels <200 mg / dL. Table 2 shows a significant decrease in scores for various DFU indicators after intervention with Cocor Bebek leaves and NaCl solution. Wilcoxon tests indicate a p value of 0.000 ≤ α = 0.05, sig- nifying significant improvement in DFU healing for both interven- tions. Additionally, the Mann-Whitney test reveals significant dif- ferences in the effectiveness of DFU healing between the Cocor Bebek leaves and NaCl groups, with a p value of 0.003 ≤ α = 0.05. Discussion After cleaning wounds with Cocor Bebek leaves, BWAT indi- cators such as wound fringe, tunnel, necrotic tissue type, exudate type, exudate count, skin color around the wound, peripheral edema, hardening of peripheral tissue, granulation tissue, and epithelialization showed decreased scores, indicating improved Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions [Healthcare in Low-resource Settings 2024;12:11835] [page 217] Non -co mmerc ial us e o nly wound conditions. Megawati’s 2023 research highlighted that Cocor Bebek leaves, containing flavonoids, saponins, and tannins, aid wound healing.25 Flavonoids act as antioxidants and anti- inflammatories, saponins stop bleeding and have antibacterial properties, while tannins counteract inflammatory mediators and possess antibacterial effects.26 Alkaloids, steroids, and terpenoids in Cocor Bebek leaves contribute to antibacterial, antiulcer, anti- fungal, antiviral, hepatoprotective, and antiseptic properties.27–29 The post-intervention group exhibited accelerated wound healing, benefiting from the multifaceted effects of Cocor Bebek leaves. BWAT assessment indicated smaller post-intervention scores, reflecting faster healing in the intervention group.27,30 Factors influencing this improvement included respondent characteristics like ages between 30-40 years, diabetes mellitus drug consump- tion, adherence to a diet, and blood sugar levels <200 mg/dL, as outlined in Table 1. After cleaning wounds with NaCl, BWAT indicators such as necrotic tissue count, exudate count, peripheral edema, and hard- ening of peripheral tissue showed decreased scores, signifying improved wound conditions. NaCl 0.9% is an isotonic, safe, non- irritant solution that preserves granulation tissue, maintains wound moisture, and aids the healing process.31 It matches the body’s salt content, preventing hypersensitivity reactions and promoting epithelial tissue development.32 NaCl 0.9% serves as a cleansing and rehydration fluid, removing excessive wound fluid and metabolic waste to create a moist environment for autolytic debridement.33 The control group, undergoing NaCl 0.9% wound cleansing, exhibited faster wound healing as indicated by BWAT scores. Post-control scores were smaller than pre-control scores, reflecting accelerated healing. Factors contributing to this improvement in the control group, outlined in Table 1, include reg- ular consumption of Diabetes Mellitus drugs and adherence to a diet by respondents.34–36 After cleaning wounds with Cocor Bebek leaves and NaCl, BWAT observations revealed differences in the rate of score decrease for indicators such as depth, wound fringe, type and num- ber of necrotic tissue, type and amount of exudate, skin color around the wound, granulation tissue, and epithelialization. Statistical tests indicated a significant difference in the effective- ness of DFU healing between the intervention group (Cocor Bebek leaf wound cleaning) and the control group (NaCl wound clean- ing). The advantage of the intervention group lies in the natural Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions Table 1. The characteristics of respondents in Surabaya Wound House, with division between intervention group (Pok) and control group (N=40). Characteristics of respondents Intervention group (%) Control group (%) Age 30-40 years 50 0 40-50 years 20 20 50-60 years 30 50 >60 years 0 30 Gender Man 55 20 Woman 45 80 Work Housewives 45 20 Farmer 0 0 Self employed 15 0 Private employees 25 0 Civil servants 0 5 Retired civil servant 0 30 Other 15 45 Years with diabetes mellitus <12 months 45 5 1-2 years 30 35 2-3 years 10 35 >3 years 15 25 History of diabetes Exist 90 95 None 10 5 Sports habits Ever 0 0 Never 100 100 DM/insulin medication consumption Yes 100 100 Not 0 0 Maintaining diet Yes 100 100 Not 0 0 Blood sugar <200 mg/dL 95 100 >200 mg/dL 5 0 [page 218] [Healthcare in Low-resource Settings 2024;12:11835] Non -co mmerc ial us e o nly compounds present in Cocor Bebek leaves, including flavonoids, saponins, tannins, alkaloids, steroids, and terpenoids, which accel- erate wound healing by reducing glucose absorption, exhibiting antibacterial, anti-inflammatory, and antiseptic properties.37,38 Saponins in Cocor Bebek leaves stop bleeding, treat wounds, and have antibacterial and anti-inflammatory effects, while tannins act as anti-inflammatory and antibacterial agents.39,40 Alkaloids, steroids, and terpenoids in Cocor Bebek leaves contribute antibac- terial, antidiabetic, and antifungal properties, further enhancing wound healing.39–41 The control group (wound cleaning with 0.9% NaCl) primarily contained 0.9% sodium and chloride compounds, serving as an isotonic fluid and physiological saline to maintain wound moisture and enhance epithelial tissue migration.42,43 Variances in compound content between the intervention (Cocor Bebek leaf wound clean- ing) and control groups influenced DFU improvement, with the intervention group exhibiting faster healing. Observations indicat- ed more effective wound cleaning in the intervention group, reflected in decreased BWAT scores across 10 out of 13 indicators, including wound fringe, tunnel, necrotic tissue type, exudate type, exudate count, skin color around the wound, peripheral edema, hardening of peripheral tissue, granulation tissue, and epithelial- ization. In contrast, the control group showed decreased scores on three indicators—number of necrotic tissues, number of exudates, and hardening of peripheral tissues. This underscores the superior effectiveness of wound cleansing with Cocor Bebek leaves com- pared to 0.9% NaCl in treating diabetic foot ulcers. External fac- tors, such as the age of diabetes mellitus sufferers in the control group exceeding one year, may impact improvements in DFU heal- ing across BWAT indicators, necessitating discussion and consid- eration based on previous studies on long-term diabetes. Conclusions Wound cleansing using Cocor Bebek leaves (Kalanchoe pinna- ta) significantly enhances the healing of diabetic foot ulcers (DFU). The utilization of Cocor Bebek leaves has demonstrated effectiveness in reducing scores on various BWAT indicators, including wound fringe, tunnel, necrotic tissue type, exudate type, exudate count, skin color around the wound, peripheral edema, hardening of peripheral tissue, granulation tissue, and epithelial- ization. This study provides evidence that Cocor Bebek leaves con- tain active compounds, such as flavonoids, saponins, tannins, alka- loids, steroids, and terpenoids, which can offer anti-inflammatory, antibacterial, antiseptic, antidiabetic effects, and accelerate wound healing. Therefore, the use of Cocor Bebek leaves can be consid- ered a potential natural alternative for cleaning wounds in diabetics with diabetic foot ulcers. References 1. Agustari F, Novitasari D, Sembayang SM. Jurnal Peduli Masyarakat. J Pengabdi Kpd Masy - Aphelion 2022;4:603–8. 2. Mboi N, Syailendrawati R, Ostroff SM, et al. The state of health in Indonesia’s provinces, 1990–2019: a systematic anal- ysis for the Global Burden of Disease Study 2019. Lancet Glob Heal 2022;10:e1632–45. 3. Apriani R, Dahlia D, Kurnia DA. Penggunaan Negative Pressure Wound Therapy (NPWT) terhadap Diabetic Foot Ulcer. J Telenursing 2023;5:1040–9. 4. Hingorani A, Lamuraglia GM, Henke P, et al. The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg 2016;63:3S-21S. 5. Faizah R, Efendi F, Suprajitno S. The effects of foot exercise with audiovisual and group support foot exercises to diabetes mellitus patients. J Diabetes Metab Disord 2021; Available from: https://www.scopus.com/inward/record.uri?eid=2-s2.0- 85101682595&doi=10.1007%2Fs40200-021-00756- 9&partnerID=40&md5=bd53e8aba3899437d7eee805f5c45d9 7 6. Huda N. Asuhan Keperawatan Diabetes Milletus dan Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions [Healthcare in Low-resource Settings 2024;12:11835] [page 219] Table 2. Statistical analysis result of BWAT indicator changes before and after intervention in experimental and control groups. BWAT indicator Intervention group Control group p Pre-test Post-test Δ Pre-test Post-test Δ Size 2 2 0 2 2 0 0.003c Depth 2 2 0 4 4 0 0.003c Wound fringe 3 1 2 4 4 0 0.003c Tunnel 3 1 2 1 1 0 0.003c Types of necrotic tissue 3 2 1 3 3 0 0.003c Number of necrotic tissues 2 2 0 5 4 1 0.003c Types of exudate 3 1 2 4 4 0 0.003c Number of exudates 2 1 1 4 3 1 0.003c Skin color around the wound 3 1 2 4 4 0 0.003c Peripheral edema 4 2 2 1 1 0 0.003c Edge hardening 3 2 1 3 2 1 0.003c Granulation network 3 2 1 5 5 0 0.003c Epithelialization 5 2 3 5 5 0 0.003c p 0.000a 0.000b aWilcoxon test of pre-post tests in the intervention group; bWilcoxon test of pre-post tests in the control group; cMann-Whitney test between the intervention and control groups. Non -co mmerc ial us e o nly Penggunaan SFE dalam Perawatan Luka Kaki Diabetes. Sidoarjo: Indomedika Pustaka; 2017. 4 p. 7. Farida I, Arini D, Mardayati RP. Efektifitas Perawatan Luka Modern Kombinasi Mendengarkan Musik Klasik Terhadap Penyembuhan Ulkus Diabetik Di Rumah Luka Surabaya. J Ilm Keperawatan Stikes Hang Tuah Surbaya 2019;13(1). 8. Faizah R, Sinawang GW, Hermanto A, Alfatih MR. Support Factors of Self Foot Care for Diabetes Mellitus Patients. J Ners 2019;14:316–20. 9. Kintoko K, Karimatulhajj H, Elfasyari TY, et al. Pengaruh Kondisi Diabetes pada Pemberian Topikal Fraksi Daun Binahong dalam Proses Penyembuhan Luka. Maj Obat Tradis 2017;22:103. 10. Fadlilah S. Faktor Faktor Yang Berhubungan Dengan Derajat Ulkus Kaki Diabetik di RSU. Moewardi Surakarta. Infokes 2018;8:37–43. 11. Ernawati DS, Surboyo MDC, Ayuningtyas NF, Nagoro AAB. Role of Inflammatory Cell Responses in Stimulating Fibroblasts in Diabetic Oral Ulcer after Treatment with Liquid Smoke of Coconut Endocarp: A Histological Assessment. Eur J Dent 2021;15:71–6. 12. Alfaqih MR, Sinawang GW, Faizah R, Hermanto A. The Management of Diabetic Foot Ulcers Using the Wound Treatment Techniques of Modern Dressing: A Systematic Review. J Ners 2019;14:176–80. 13. Nurbaya N, Tahir T, Yusuf S. Peranan Pencucian Luka Terhadap Penurunan Kolonisasi Bakteri Pada Luka Kaki Diabetes. J Keperawatan Muhammadiyah 2018;3:110–5. 14. Junaidi, Haryanto, Kardiatun T. Pengaruh pembalut wanita ter- hadap terjadinya maserasi pada luka kronik diabetic foot ulcer. J Perawat Indones 2022;6:1211–22. 15. Faizah R, Efendi F, Suprajitno S. A Systematic Review of Foot Exercises with Group Support to Improve the Foot Health of Diabetes Mellitus Patients. J Ners 2020;15:129–34. 16. Munawwarah M, Neonbasu MA, Lesmana SI. Penatalaksanaan Fisioterapi Pada Kasus Diabetic Foot Ulcer Di Rumah Luka Surabaya (Sidoarjo). Indones J Physiother Res Educ IJOPRE 2022;3:62–74. 17. Diwanti AP, Lestari N, A EI. Pengaruh Ekstrak Daun Cocor Bebek (Kalanchoe Pinnata) 50% Terhadap Waktu Penyembuhan Luka Sayatan Pada Mukosa Rongga Mulut Tikus Wistar. IJOH Indones J Public Heal 2023;1:281–5. 18. Mustamu AC, Mustamu HL, Hasim NH. Peningkatan Pengetahuan & Skill Dalam Merawat Luka. J Pengabdi Masy Sasambo 2020;1:103. 19. Sawitri PA, Dewi WCS, Amalia AR, Sudayasa IP, Agastia G. COBEK ANTIK: Pengaruh Ekstrak Daun Cocor Bebek (Kalanchoe pinnata) Terhadap Kadar Gula Darah Tikus Model Diabetik. Medula 2019;6. 20. Putri AH, Putriyana RS, Silviani N. Isolasi dan Ekstraksi Kelompok Senyawa Flavonoid dari Ekstrak Daun Cocor Bebek (Kalanchoe pinnata). Fuller J Chem 2019;4:28. 21. Putriani K. Aktivitas Antibakteri Ekstrak Metanol Daun Cocor Bebek (Kalanchoe Pinnata (Lam.) Pers.) Terhadap Propionibacterium Acnes dan Staphylococcus Aureus. J Biog 2023;8:412–8. 22. Umeh VN, Ilodigwe EE, Ajaghaku DL, Erhirhie EO, Moke GE, Akah PA. Wound-healing Activity of the Aqueous Leaf Extract and Fractions of Ficus exasperata (Moraceae) and its Safety Evaluation on Albino Rats. J Tradit Complement Med 2014;4:246–52. 23. Purwanitiningsih E, Lestari D. Uji Aktivitas Antibakteri Ekstrak Daun Cocor Bebek (Kalanchoe Pinnata (Lam)) Terhadap Pertumbuhan Bakteri Salmonella typhi Dengan Metode Kirby Bauer. J Ilm Kesehat 2020;12:142–8. 24. Cholid Z, Prasetya RC, Sukamto BRP. Efektivitas ekstrak daun cocor bebek (kalanchoe pinnata) terhadap waktu perdarahan (bleeding time) pada ekor mencit strain balb-c Effectiveness of kalanchoe pinnata leaf extract on bleeding time in the tail of balb-c mice strain. Padjadjaran J Dent Res Students 2022;6:144. 25. Megawati M, Oktarlina RZ. Studi Literatur:Cocor Bebek (Kalanchoe pinnata) sebagai penyembuhan luka bakar. J ilmu Kesehat Kedokt 2023;10:1489–93. 26. Fitri Yani D. The Anti-Inflammatory Potential Of Cocor Bebek Leaves (Kalanchoe pinnata L) Against In Vitro Protein Denaturation. Spin 2021;3:12–21. 27. Saputra TR, Ngatin A. Ekstraksi Daun Cocor Bebek Menggunakan Berbagai Pelarut Organik Sebagai Inhibitor Korosi Pada Lingkungan Asam Klorida. Fuller J Chem 2019;4:21. 28. Sabrina AP, Tania E, Nurhalifah N, Veronita SC, Puji SI, Nuryamah S. Aktivitas Imunodulator Dari Jawer Kotok (Coleus Scutellariodes (L) Benth). J Buana Farma 2022;2:40– 55. 29. Gitafitri F, Kurniawan ST, Vioneery D. Pengaruh Gel Daun Jambu Mete (Anacardium Occidentale L.) Terhadap Perawatan Luka Bakar Grade II Pada Hewan Uji Mencit (Mus Musculus). Universitas Kusuma Husada Surakarta; 2023. 30. Gunawan A, Selvina D, Rosdiana. Potensi Efek Antibakteri Tinta Cumi (Loligo Sp.) dan Sotong (Sepia Sp.) Pratista Patologi. Pratista Patol 2023;8(2). 31. Shantika SS, Kusdiantini A. Pemeriksaan Laju Endap Darah Metode Westergren Menggunakan Natrium Sitrat 3,8% dan Edta yang ditambah Nacl 0,85%. Innov J Soc Sci Res 2023;3:3111–9. 32. Nurman M. Perbandingan Efektifitas Madu + NaCl 0,9% Dengan Nacl 0,9 % Saja Terhadap Penyembuhan Luka Gangren Pada Pasien Diabetes Mellitus Tipe II Di Wilayah Kerja Puskemas Bangkinang Kota Tahun 2015. J Keperawatan STIKes Tuanku Tambusai Riau 2015;16:1–37. 33. Suriani A, Syaharuddin S, Damayanty ST, Fardi F. Penerapan Pembersihan Luka Dengan Menggunakan NaCl 0.9% Untuk Menghindari Kerusakan Integritas Kulit Pada Pasien yang Mengalami Ulkus Diabetik. J Ilm Kesehat Sandi Husada 2023;12:459–66. 34. Akoit EE, Efendi F, Dewi YS. Impact of diabetes self-manage- ment education in middle-aged patients with type 2 diabetes mellitus: A systematic review. Gac Med Caracas 2022;130:S1183–95. 35. Rokhmad K, Supriyanto S. Analysis of PROLANIS activities on controlling type-2 diabetes mellitus at Puskesmas Tulungagung in 2022. J Public Health Africa 2023;14:2617. 36. Kusnanto K, Alfaqih M, Padoli P, Arifin H. A qualitative study inquiry among patients with diabetic foot ulcers: What have they felt? Open Access Maced J Med Sci 2021;9:574–80. 37. Qomaliyah EN, Indriani N, Rohma A, Islamiyati R. Skrining Fitokimia, Kadar Total Flavonoid dan Antioksidan Daun Cocor Bebek Phytochemical Screening, Total Flavonoids and Antioxidants of Kalanchoe Pinnata Linn. Leaves. Curr Biochem 2023;10:1–10. 38. Ayyun K, Khafidz Y, Rosydah I, et al. Profil Studi Fitokimia Dan Aktivitas Farmakologi Buah Mangga (Mangifera Indica L.). Farmaka 2023;01:60–8. 39. Wulandari PAC, Ilmi ZN, Husen SA, et al. Wound healing and antioxidant evaluations of alginate from sargassum ilicifolium Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions [page 220] [Healthcare in Low-resource Settings 2024;12:11835] Non -co mmerc ial us e o nly and mangosteen rind combination extracts on diabetic mice model. Appl Sci 2021;11:4651. 40. Ilmi ZN, Wulandari PAC, Husen SA, et al. Characterization of alginate from sargassum duplicatum and the antioxidant effect of alginate-okra fruit extracts combination for wound healing on diabetic mice. Appl Sci 2020;10:6082. 41. Hayon MFK, Supriningrum R, Fatimah N. Identifikasi Jenis Saponin Dan Uji Aktivitas Antibakteri Ekstrak Metanol Kulit Batang Sekilang (Embelia Borneensis Scheff.) Terhadap Bakteri Pseudomonas Aeruginosa ATCC 9027 Dan Streptococcus Mutans ATCC 25175. J Ris Kefarmasian Indones 2023;5:258–72. 42. Fernandez R, Green HL, Griffiths R, et al. Water for wound cleansing. Cochrane database Syst Rev 2022;9:CD003861. 43. Ramirez-Acuña JM, Cardenas-Cadena SA, Marquez-Salas PA, et al. Diabetic Foot Ulcers: Current Advances in Antimicrobial Therapies and Emerging Treatments. Antibiot (Basel, Switzerland) 2019;8:193. Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions [Healthcare in Low-resource Settings 2024;12:11835] [page 221] Non -co mmerc ial us e o nly