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"Pendahuluan: Aktivitas proliferasi, sintesis kolagen, dan hidrasi kulit akan menurun seiring proses penuaan kulit, sehingga kulit menua menjadi kusam, kendur, dan kering. Aquaporin-3 (AQP3) adalah protein kunci yang berperan pada proliferasi dan hidrasi keratinosit, sekarang menjadi target inovasi pengembangan kosmetika pelembab anti penuaan kulit. Penelitian ini bertujuan menganalisis kombinasi dua bahan alam yaitu ekstrak etanol Centella asiatica dan nanopartikel kitosan (EECA+NPK) terhadap proliferasi sel fibroblast dan keratinosit, sintesis kolagen I dan III serta ekspresi protein aquaporin-3 (AQP3) secara in vitro.Metode: Dilakukan uji proliferasi sel fibroblas dan keratinosit yang dianalisis dengan uji Microculture Tetrazolium (MTT), analisis sintesis kolagen I dan III menggunakan Enzyme Linked Immunosorbent Assay (ELISA) kit (COL1A1 dan COL3A1) setelah dipajankan dengan ekstrak etanol Centella asiaticadalam nanopartikel kitosan (EECA + NPK) pada beberapa konsentrasi selama 24, 48, dan 72 jam dibandingkan dengan asam retinoat, selanjutnya ekspresi aquaporin-3 (AQP3) dianalisis dengan teknik Imunositokimia menggunakan antibodi anti-aquaporin3 ab125219, kemudian dianalisis secara kuantitatif menggunakan ImageJ software.Hasil: EECA + NPK dapat meningkatkan proliferasi fibroblas 1.6 kali lipat dibandingkan kontrol. Optimal pada konsentrasi 6.25 mg/mL dan proliferasi sel keratinosit optimal pada konsentrasi 3.125 mg/mL, secara statistic tidak berbeda bermakna dengan AR. (EECA + NPK) dapat meningkatkan sintesis kolagen I setelah pajanan 72 jam dan kolagen III setelah pajanan 48 jam, secara statistic tidak berbeda bermakna dengan AR. Uji imunositokimia dengan antibodianti-aquaporin3 ab125219 (EECA + NPK) dapat meningkatkan ekspresi aquaporin 3 (AQP 3) pada sel fibroblas optimal pada konsentrasi 12.5 mg/mL dan sel keratinosit pada konsentrasi3.125 mg/mL setelah pajanan selama 24 jam, secara statistik berbeda dengan AR.Kesimpulan: Ekstrak etanol Centella asiatica dalam nanopartikel kitosan (EECA + NPK) dapat meningkatkan proliferasi fibroblas dan keratinosit, meningkatkan sintesis kolagen I dan III, serta ekspresi protein AQP3 pada sel fibroblas dan sel keratinosit.

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Introduction: Proliferation activity, collagen synthesis, and hydration of the skin will decrease with the process of aging, therefore, skin looks dull, sagging, and dry. Aquaporin-3 (AQP3) is a key protein that plays a role in keratinocyte proliferation and hydration, recently becomes the target of innovation development of anti-aging cosmetic moisturizer. This research aims to analyze a combination of two natural ingredients, Centella asiaticaethanolic extractand chitosan nanoparticles (EECA + NPK) to increased proliferation fibroblast cell and keratinocyte, synthesis type I and III collagen, and the expression of AQP3 in vitro.Methods: Microculture Tetrazolium Test was conducted to analyze the proliferation of fibroblast and keratinocyte. The synthesis of type I and III collagen in fibroblast were analyzed using Ezyme Linked Immunosorbent Assay (ELISA) kit (COL1A1 and COL3A1) after the exposure of CAEE + CNP in several concentrations for 24, 48, 72 hours and compared to Retinoic acid (RA). The expression of AQP 3 on fibroblast and keratinocyte was analyzed using antibody anti-aquaporin 3 ab125219 immunocytochemistry technique, then quantitively analyzed using Image-J software.Results: CAEE+ CNP increased the proliferation of fibroblas optimal result at 6.25mg/mL concentration and the proliferation of keratinocyte increased 1.5 time than control, optimal result at 3.125 mg/mL concentration, statistically were not significant different with RA.CAEE + CNP increased the synthesis collagen type I optimal after incubated for 72hours and the synthesis collagen type III optimal 48 hours, statistically were not significant different with RA.Using antibody anti-aquaporin 3 ab125219 immunocytochemistry examination indicated CAEE+ CNP increased the expression of AQP 3 on fibroblast and keratinocyte, optimal results at 12.5 mg/mL and 3.125 mg/mL respectively after 24 hours exposure.Conclusion: CAEE + CNP increased the proliferation of fibroblast and keratinocyte, synthesis of type I and III collagen, and the expression of AQP3 in fibroblast and keratinocyte;Introduction: Proliferation activity, collagen synthesis, and hydration of the skin will decrease with the process of aging, therefore, skin looks dull, sagging, and dry. Aquaporin-3 (AQP3) is a key protein that plays a role in keratinocyte proliferation and hydration, recently becomes the target of innovation development of anti-aging cosmetic moisturizer. This research aims to analyze a combination of two natural ingredients, Centella asiaticaethanolic extractand chitosan nanoparticles (EECA + NPK) to increased proliferation fibroblast cell and keratinocyte, synthesis type I and III collagen, and the expression of AQP3 in vitro."

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Menopause menyebabkan hipoestrogenisme dan mengakibatkan penuaan kulit. Fitoestrogen dari biji T. foenum-graecum (klabet) diharapkan dapat mengatasi penuaan kulit pascamenopause. Penelitian ini bertujuan untuk mengetahui konsentrasi optimal ekstrak klabet dalam menstimulasi sekresi COL1A1 dan COL3A1, cara kerjanya melalui jalur reseptor estrogen α (REα) atau REβ, dan peran klabet dalam mengurangi kerutan serta meningkatkan ketebalan kulit wajah.

Studi in vitro menggunakan human dermal fibroblast (HDF) tua yang diperoleh dari kultur sel fibroblas kulit perempuan pascamenopause dan HDF muda dari prepusium, dilakukan di Laboratorium Universitas YARSI. Sekresi COL1A1 dan COL3A1 diperiksa dengan ELISA lalu ditambah antagonis REa dan b. Penelitian in vivo merupakan uji klinis acak tersamar ganda berdurasi 12 minggu, di RSCM, Januari–November 2019. Subjek 50 perempuan pascamenopause yang dibagi dua: kelompok perlakuan mendapat krim klabet 5% dan kelompok plasebo mendapat krim dasar. Skor kerutan dahi, crow’s feet, dan nasolabial diukur dengan skoring atlas skin aging Bazin dan tebal dermis dengan high resolution ultrasound (HRU) 18 MHz.

Ekstrak klabet 2 µg/mL merupakan konsentrasi optimal dalam meningkatkan sekresi COL1A1 dan COL3A1 pada HDF tua dan muda dibandingkan tanpa perlakuan dan 5 nM estradiol. Uji inhibisi menunjukkan hambatan REα 50%; REβ dan RE α,β sampai 75%. Penurunan skor kerutan dahi, crow’s feet, dan nasolabial berbeda bermakna pada kedua kelompok minggu ke-4, ke-8, dan ke-12.  Peningkatan selisih skor kerutan dahi, crow’s feet, dan nasolabial tidak bermakna pada kedua kelompok antara baseline, minggu ke-4, ke-8, dan ke-12. Ketebalan dermis meningkat bermakna pada minggu ke-4 dibandingkan baseline. Pada minggu ke-8 dibandingkan minggu ke-4 dan pada minggu ke-12 dibandingkan minggu ke-8, ketebalan dermis menurun bermakna pada kedua kelompok. Peningkatan selisih ketebalan dermis pada minggu ke-4 dan ke-8 tidak bermakna.

Simpulan: Ekstrak klabet 2 µg/mL meningkatkan COL1A1 dan COL3A1 lebih banyak dibandingkan kelompok tanpa perlakuan dan estradiol 5 nM. Klabet bekerja terutama melalui REβ. Penurunan skor kerutan kulit dan peningkatan ketebalan kulit wajah tidak bermakna dibandingkan plasebo. Diduga, krim klabet konsentrasi 5% tidak tepat untuk mengurangi kerutan dan menambah ketebalan kulit. Perlu penelitian lebih lanjut untuk mengetahui konsentrasi optimal klabet sebagai terapi penuaan kulit wajah pascamenopause.

 

Kata kunci: COL1A1, COL3A1, kerutan kulit, ketebalan dermis, klabet, pascamenopause, penuaan kulit wajah, Trigonella foenum-graecum.

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Hypoestrogenism in menopause leads to skin aging, for which phytoestrogen originated from the seeds of T. foenum-graecum (fenugreek) is expected to be a solution. This study aims to show the effect of phytoestrogen from fenugreek extract in stimulating COL1A1 and COL3A1 through its mechanism of action on estrogen receptor (ER) ERa or ERb and its role in diminishing facial wrinkles and increasing dermal thickness.

The in vitro study was carried out in YARSI University Laboratory throughout March 2017–March 2018. This study looks into the effect of fenugreek extract on collagen level secretion in old and young human dermal fibroblast (HDF) compared to control. The in vivo study was a randomized, double-blind, 12-week trial conducted in RSCM from January–November 2019. Fifty postmenopausal women divided into two groups: the intervention group was given 5% fenugreek cream while the placebo group was given base cream.

The in vitro study showed that a concentration of 2 mg/mL was the optimal dose to stimulate COL1A1 and COL3A1 secretion in both old and young HDF compared to control (no treatment) and 5 nM estradiol. The inhibition test demonstrated suppression of ERa by 50%; ERb and ERa,b by up to 75%, indicating that the fenugreek activates both receptors, especially ERb. However, the success of the in vitro study did not translate into the in vivo study. Both the intervention group and the placebo group were able to achieve statistically significant in facial wrinkle scores from all focus areas without any significant disparity between both groups at all timepoints. Dermal thickness of facial skin showed similar results for both groups with significant improvements in the 8^thweek compared to baseline and significant decrease by the 12^thweek.

Conclusion: Fenugreek extract with a concentration of 2 mg/mL increased COL1A1 and COL3A1 secretion more potently compared to control and estradiol 5 nM. However, the decrease in facial skin wrinkles scores and the increase in dermal thickness were not significant compared to placebo. We suspect that a concentration of 5% was not adequate for the expected antiaging effects. Further studies are necessary to determine a more appropriate fenugreek concentration to permit clinical use as a postmenopausal antiaging therapy.

 

Keywords: COL1A1, COL3A1, dermal thickness, fenugreek, postmenopausal women, facial skin aging, skin wrinkles, Trigonella foenum-graecum.

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Kelainan kulit kering banyak ditemukan pada penyandang DMT2. Patogenesis kulit kering pada DMT2 dipicu oleh kondisi hiperglikemia kronik yang meningkatkan Advanced glycation end products (AGE) N(6)-carboxymethyl-lysine (CML), sitokin proinflamasi dan stres oksidatif.  Kombinasi Centella asiatica  oral  (CAo) dan topikal (CAt) diduga dapat meningkatkan efektivitas tatalaksana kulit kering DMT2. Penelitian bertujuan menganalisis efektivitas dan keamanan kombinasi CAo + CAt dalam memperbaiki kulit kering DMT2.

 

Penelitian merupakan uji klinis acak tersamar ganda di Poliklinik Metabolik Endokrin Departemen Penyakit Dalam RSCM dan 5 puskesmas di Jakarta pada bulan Juli 2018–Maret 2019. Subjek dibagi menjadi 3 kelompok, yaitu kelompok CAo + CAt, plasebo oral (Plo) + CAt, dan Plo + Plasebo topikal (Plt) masing-masing berjumlah 53 orang. Perbaikan kulit kering secara klinis diukur dengan Specified Symptom Sum Score (SRRC) dan Skin Capacitance (SCap). Perbaikan secara molekular diukur  CML, IL-1a, dan aktivitas superoksida dismutase (SOD). Keamanan kombinasi CAo + CAt dilakukan melalui penilaian efek simpang oral dan topikal.

 

Pada ketiga kelompok, median HbA1c > 7%. Glukosa darah sewaktu (GDS) kelompok CAo + CAt hari ke-15 dan 29 semakin menurun. Efektivitas kombinasi CAo + CAt dinilai melalui analisis subgrup berdasarkan nilai HbA1c dan GDS. Pada glukosa darah terkontrol baik, persentase penurunan SRRC lebih besar pada kelompok CAo + CAt vs Plo + Plt (p = 0,04). Peningkatan SCap kelompok CAo + CAt lebih besar dibandingkan Plo + Plt (p = 0,01). Pada glukosa darah terkontrol kurang baik peningkatan SOD kelompok CAo + CAt lebih besar dibandingkan Plo + Plt  (p = 0,01). Tidak terdapat korelasi antara CML, IL-1α dan SOD dengan SRRC atau SCap. Terdapat korelasi sedang sampai kuat dan arah korelasi sesuai antara CML dengan SOD (r = 0,58, p < 0,05)  dan  IL-1α dengan SOD (r = 0,70, p < 0,05) pada glukosa darah terkontrol baik. Tidak terdapat efek simpang oral dan topikal yang bermakna pada penggunaan CAo + CAt dibandingkan 2 kelompok.

 

Simpulan: Pada glukosa darah terkontrol baik, perbaikan SRRC dan SCap  kelompok CAo + CAt lebih besar dibandingkan Plo + Plt.  Pada glukosa darah terkontrol kurang baik peningkatan SOD kelompok CAo + CAt lebih besar daripada Plo + Plt. Terdapat korelasi sedang sampai kuat antara CML atau IL-1α dengan SOD pada glukosa darah terkontrol baik. Tidak terdapat efek simpang oral dan topikal yang bermakna pada kelompok CAo + CAt dibandingkan 2 kelompok.

 

Kata kunci: CML, DMT2, IL-1a, kulit kering, SCap, SOD, SRRC

 

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Dry skin is a common findings in type 2 diabetes mellitus (T2DM). The pathogenesis of dry skin in T2DM rises from chronic hyperglycemic condition which causes an increase in levels of Advanced glycation end products (AGEs)  N(6)-carboxymethyl-lysine (CML), pro-inflammation cytokines and oxidative stress. Combination of oral and topical Centella asiatica (CA) is expected to ameliorate dry skin in T2DM patients more effectively.

 

This study was a double blinded randomized clinical trial in T2DM patients with dry skin in outpatients clinic of Metabolic Endocrine, Internal Medicine Department, dr. Cipto Mangunkusumo Hospital, and 5 primary health cares in Jakarta from July 2018 to March 2019. The subjects were divided into three groups, CA oral (CAo) + CA topical (CAt) group, oral placebo (Plo) + CAt group, and Plo + topical placebo (Plt) which included 53 subjects respectively. Dry skin improvement was evaluated clinically using Specified Symptom Sum Score (SRRC) and Skin Capacitance (SCap). The molecular improvement was evaluated using levels of CML, inflammation interleukin 1-α (IL-1α) concentration, and oxidative stress superoxide dismutase (SOD).

 

In the three groups, median of HbA1c > 7%. Random blood glucose (RBG) in CAo + CAt group in day-15 and 29 were further decreased. Effectivity of CAo + CAt combination were assessed via subgroup analysis based on HbA1c and RBG. In well controlled blood glucose, on day-29, percentage of SRRC decrement was greater in  CAo + CAt compared to control group without CA (p = 0,04). SCap value in CAo + CAt group was greater than control group (p = 0,01). In the partially controlled blood glucose, increment of SOD activity of CAo + CAt group was greater than control group (p = 0,01). There was no correlation found between CML, IL-1α and SOD with SRRC nor SCap. There were medium to strong correlation between CML with SOD (r = 0,58, p < 0,05)  and IL-1α with SOD (r = 0,70, p < 0,05)  in well controlled blood glucose. Systemic and topical adverse events were not found significantly in CAo or CAt usage compared to the other two groups.

 

Conclusion: In well controlled blood glucose, improvement of SSRC and SCap in CAo + CAt were greater than Plo + Plt.  In partially controlled blood glucose,  increment of SOD in CAo + CAt was greater than Plo + Plt.  There was moderate to strong correlation between CML or IL-1 and SOD in well controlled blood glucose. There were no significant adverse events found due to CAo + CAt compared to the other 2 group in the study.

 

Keywords: CML, diabetes mellitus, dry skin, IL-1a, SCap, SOD, SRRC

 

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"Latar Belakang: Alopesia androgenetik (AAG), merupakan kelainan rambut yang mengganggu secara psikososial bagi sebagian besar lelaki. Pengobatan yang ada saat ini masih terbatas. Kinin secara empirik telah digunakan sebagai zat penumbuh rambut. Namun belum ada penelitian untuk menilai mekanisme kerja dan efektivitas kinin topikal terhadap pertumbuhan rambut.Metode: Kajian in silico molecular docking dan molecular dynamic simulation dilakukan untuk menilai afinitas kinin terhadap enzim 5α-reduktase dengan kontrol finasterid. Uji hambatan kinin terhadap 5α-reduktase secara in vitro dinyatakan sebagai nilai IC50 kinin, dengan finasterid sebagai pembanding. Pada percobaan in vivo, 28 ekor mencit C57BL/6 dibagi secara acak menjadi 7 kelompok terdiri dari 4 ekor. Kelompok (A) testosteron (alopesia),yang di suntik 1 mg testosteron secara subkutan,(B) testosteron+finasterid 2%(C) kelompok normal, dan kelompok (D-G) testosteron+kinin 0,5%,1%,1,5% dan 2 %. Dioles bahan uji sesuai kelompok setiap hari selama 28 hari. Luas dan panjang rambut dinilai secara visual setiap minggu. Pemeriksaan histologi (morfologi dan kepadatan folikel rambut), pemeriksaan imunohistokimia kaspase-3, pemeriksaan ELISA PGE2 dan pemeriksaan MDA dilakukan setelah 28 hari. Hasil : Hasil in silico menunjukkan kinin mempunyai afinitas yang cukup baik terhadap 5β-reduktase, meskipun lebih rendah dibanding finasterid (ΔG kinin -31,67 kj/mol dan ΔG finasterid -42,89 kj/mol dari hasil penambatan molekuler; serta ΔG kinin -6,32±12,84 kj/mol dan ΔG finasterid -11,17±18,92 kj/mol dari hasil simulasi dinamika molekuler. Hasil pengukuran hambatan enzim 5α-reduktase didapatkan IC50 kinin 10,6 ±1,40 uM dan IC50 finasterid 0,623 ± 0,14 nM. Luas area pertumbuhan rambut semua kelompok perlakuan kinin lebih luas dibandingkan kelompok alopesia dan berbeda bermakna pada pada minggu ke-3 dan ke-4. Gambaran histopatologi morfologi rambut semua kelompok didominasi fase anagen . Rasio anagen: telogen kelompok perlakuan kinin lebih tinggi dibandingkan kelompok alopesia. Kepadatan folikel rambut kelompok perlakuan kinin lebih tinggi secara bermakna daripada kelompok alopesia. Kinin 0,5%, 1%, dan finasterid menurunkan ekspresi kaspase-3. PGE2 meningkat pada semua kelompok perlakuan kinin, tertinggi pada kinin 2%. dan berbeda bermakna terhadap kelompok alopesia. Pemberian kinin tidak mampu menurunkan kadar MDA.Kesimpulan: Pemberian kinin pada mencit jantan yang diinduksi testosteron mempunyai efek menumbuhkan rambut, meningkatkan kepadatan folikel rambut. Kinin menghambat enzim 5α-reduktase, meningkatkan kadar PGE2, menurunkan ekspresi Kaspase-3, tetapi tidak menurunkan MDA. Kinin potensial dikembangkan sebagai penumbuh rambut.Background: Androgenetic alopecia (AGA), is a hair disease which lead to negative psychological effects in most of its sufferers. Currently, treatments of AGA are limited to topical minoxidil and oral finasterid, which possess many side effects. Quinine had empirically used as herbal hair grower, but its mechanism of action and effectiveness are not studied yet.Methods: Molecular docking was done to analyse the inhibition affinity of the 5β-reductase enzyme of both quinine and finasteride as control. Further, an in vitro test for inhibition of 5α-reductase was carried out by measuring the IC50 on both compounds. The experimental study used male C57BL/6 mice aged 7 weeks. Mice were randomly divided into 7 groups of 4 animals, namely (A) testosterone (alopecia group) which was performed subcutaneous injection of 1 mg testosterone on the back of mice (B) testosterone+2% finasterid, (C) normal group, (D-G) testosterone+0.5%, 1% , 1.5% and 2% quinine. Application of the test material on the back of the mice was carried out daily for 28 days. Hair growth assessment was done visually by assessing hair growth area every week. Histologic examination ( hair morphology and density of hair follicles), immunohistochemical examination of caspase-3, ELISA examination for PGE2, and lipid peroxidase by MDA examination were carried out after 28 days.Results: The results of molecular docking showed that quinine had a good affinity for 5β-reductase, but it was lower than finasterid (ΔG quinine = -31.67 kJ/mol vs ΔG finasterid = 42.89 kJ/mol and from dynamic simulation ΔG quinine -6,32±12,84 kj/mol and ΔG finasteride -11,17±18,92 kj/mol). The IC50 of quinine was 10.6 ± 1.40 uM, while finasterid was 0.623 ± 0.14 nM.The area of hair growth in the quinine treatment group was wider than the alopecia group and showed significance on the 3rd and 4th week. Histopathological features all of the groups was dominated by the anagen phase. The anagen:telogen ratio of the alopecia group was lower than that of the quinine group. The density of hair follicles in the treatment group and the alopecia group was statistically significant.The administration of 0.5% and 1% quinine, as well as finasterid, decreased the expression of caspase-3. PGE2 was increased in the quinine treatment group and significant compared to the alopecia group. MDA levels were higher in quinine compared to alopecia group.Conclusion: Quinine was efficacious in promoting hair growth in AGA mouse models. It is inhibited 5α-reductase enzyme, increasing PGE2, decreasing caspase-3. However it was unable to suppress MDA levels. Hence, topical quinine has the potential to be further developed into a herbal medicine for hair growth."

"Diabetes sering menyebabkan komplikasi ulkus kaki diabetik (UKD) yang penyembuhannya terhambat pada fase inflamasi dan terjadi gangguan pada pembentukan jaringan granulasi. LL-37 memiliki aktivitas antimikrobial, memicu angiogenesis, serta migrasi dan proliferasi keratinosit. Penelitian ini menganalisis pengaruh krim LL-37 terhadap kecepatan penyembuhan UKD derajat ringan dengan mengkaji IL-1a, TNF-a, serta pola dan jumlah kolonisasi bakteri aerob.Penelitian ini adalah uji klinis buta ganda acak yang dilaksanakan Januari 2020–Juni 2021 di RSUPN dr. Cipto Mangunkusumo dan RSUP Persahabatan, Jakarta. Subjek adalah penyandang UKD tanpa infeksi atau infeksi derajat ringan, berusia 18–60 tahun, ABI 0,9–1,3, luas luka ≥ 2 cm2, kedalaman luka sampai dengan subkutis, dan tanpa infeksi sistemik. Subjek dibagi menjadi kelompok krim LL-37 dan plasebo yang dioles dua kali seminggu selama 4 minggu. Dilakukan pengamatan luka pada akhir minggu dengan metode planimetri dan fotografi digital lalu diolah dengan ImageJ. Subjek diperiksa kadar IL-1a dan TNF-a cairan luka dengan metode ELISA dan kultur bakteri aerob dari apusan luka pada setiap akhir minggu.Kadar LL-37 cairan luka pada kelompok LL-37 adalah 1,07 (0,37–4,96) ng/mg protein dan plasebo sebesar 1,11 (0,24–2,09) ng/mg protein (p = 0,44). Penurunan luas luka pada hari ke-14, ke-21, dan ke-28 dibandingkan hari ke-1 pada kelompok LL-37 lebih besar daripada plasebo, walaupun tidak bermakna. Pada kelompok LL-37 terjadi peningkatan luas jaringan granulasi yang lebih besar daripada plasebo pada semua hari, walaupun hanya bermakna pada hari ke-14 yaitu 0,95 (±1,34) cm2 pada kelompok LL-37 dibandingkan -0,24 (±1,01) cm2 pada kelompok plasebo (p = 0,020). Terjadi peningkatan indeks granulasi yang secara konsisten lebih besar dan bermakna (p < 0,05) pada kelompok LL-37 dibandingkan plasebo pada semua hari. Tidak terjadi penurunan kadar IL-1a dan TNF-a yang lebih besar pada kelompok LL-37. Pada hari ke-1, frekuensi bakteri aerob terbanyak adalah S. aureus yaitu 37,1% pada kelompok LL-37 dan 45% pada kelompok plasebo. Penurunan jumlah koloni bakteri pada kelompok plasebo lebih besar dibandingkan dengan kelompok LL-37 pada hari ke-28 dibandingkan dengan hari ke-1, walaupun tidak bermakna (p = 0,98).Simpulan: Kadar LL-37 pada UKD kedua kelompok rendah. Pemberian LL-37 mempercepat penyembuhan UKD tanpa infeksi maupun derajat ringan dengan meningkatkan indeks granulasi. Pemberian LL-37 tidak menurunkan kadar IL-1a dan TNF-a pada UKD. Pemberian LL-37 tidak memengaruhi pola dan jumlah kolonisasi bakteri aerob pada UKD.

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Diabetes often causes DFU (diabetic foot ulcer). Wound healing in DFU has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream on wound healing rate in DFU with mild infection by examining IL-1a, TNF-a, and aerobic bacteria colonization.

This study was a randomized double-blind controlled trial conducted from January 2020–June 2021 at RSUPN dr. Cipto Mangunkusumo and RSUP Persahabatan, Jakarta. Subjects were patients with uninfected DFU or DFU with mild infection according to IDSA, aged 18–60 years old, ABI 0.9–1.3, wound area ≥ 2 cm2, wound no deeper than subcutaneous layer, and without systemic infection. Subjects were divided into the LL-37 cream and placebo cream group which were applied twice a week for 4 weeks. Wounds were measured at the end of every week using planimetric method and digital photography and subsequently processed with ImageJ. The levels of IL-1a and TNF-a from wound fluid were measured using the ELISA method and aerobic bacteria culture was performed using wound swabs.

The level of LL-37 from wound fluid in the LL-37 group was 1.07 (0.37–4.96) ng/mg protein and in the placebo group was 1.11 (0.24–2.09) ng/mg protein (p = 0.44). The decrease in wound area on day 14, 21, and 28 compared to day 1 in the LL-37 group was greater than in the placebo group, although the difference was not significant. In the LL-37 group, there was a greater increase in granulation tissue area than in the placebo group on each day, although the difference was only significant on day 14 which was 0.95 (±1.34) cm2 in the LL-37 group compared to -0.24 (± 1.01) cm2 in the placebo group (p = 0.020). There was a consistently and significantly greater increase in granulation index (p < 0.05) in the LL-37 group compared to placebo group on each day. There was no greater decrease in IL-1a and TNF-a levels in the LL-37 group. On day 1, the highest frequency of aerobic bacteria was S. aureus which was 37.1% in the LL-37 group and 45% in the placebo group. The decrease in the number of bacterial colonies in the placebo group was greater than in the LL-37 group on day 28 compared to day 1, although the difference was not significant (p = 0.98).

Conclusion: The level of LL-37 in DFU was low in both groups. Administration of LL-37 accelerated the healing of uninfected DFU or DFU with mild infection by increasing the granulation index. Administration of LL-37 did not reduce the levels of IL-1a and TNF-a in DFU. Administration of LL-37 did not affect the pattern and number of colonization of aerobic bacteria in DFU."