Anti-inflammation and Anti-tyrosinase effect of Robusta coffee BP-42 extract gel on clinical appearance after skin grafting in long evans rats


Ulfa Elfiah1,2, David Sontani Perdanakusuma3, Iswinarno Doso Saputro3, Misnawi4

1Faculty of Medicine, Universitas Jember, Jalan Kalimantan No. 37, Jember, East Java, Indonesia.

2Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga,

Jl. Mayjen. Prof. Dr. Moestopo 47 Surabaya, East Java, Indonesia.

3Reconstructive And Aesthetic Plastic Surgery, Faculty of Medicine, Universitas Airlangga,

Jl. Mayjen. Prof. Dr. Moestopo 47 Surabaya, East Java, Indonesia.

 4Indonesian Coffee and Cocoa Research Institute, Jl. PB. Sudirman 90, Jember, East Java, Indonesia.

*Corresponding Author E-mail:,



This study compares the anti-hyperpigmentation activity of kojic acid and Robusta BP-42 coffee bean extract on skin-grafted rats. Kojic acid is one of the standards for reducing pigmentation on the skin. But, kojic acid usage presents side effects for some patients, such as skin irritation, redness, and itching. Robusta BP-42 is one of the best robusta coffee strains found in Indonesia. The Indonesian Coffee and Cocoa Research Institute, Jember Regency, East Java, provides this coffee. BP-42 coffee has the highest quality grain and organoleptic score compared to other strains. Three groups of grafted skin on long Evans rats were treated with 2% kojic acid gel (positive control), 5% robusta BP-42 coffee extract gel, and placebo gel (negative control). Observation occurred for 21 days. The photos of grafted skin were taken on days 0, 4, 7, 11, 18 and 21. Skin pigmentation was measured using ImageJ software. Histological examination was performed on days 7, 14, and 21 for all treatment groups. These histological preparations were stained with Masson Fontana. The result showed that Robusta BP-42 coffee extract gel showed a similar clinical and histological measurement to positive control. Robusta BP-42 coffee can be a new candidate to treat hyperpigmentation after skin graft surgery


KEYWORDS: Coffee, Hyperpigmentation, Robusta, BP-42, Tyrosinase.




One of the most excellent methods for wound healing is the skin graft. This procedure offers patients exceptional benefits and presents some an issue like hyperpigmentation. Particularly, if it occurs on the face and neck, hyperpigmentation becomes a severe cosmetic problem. It may cause the skin to become darker in color. Furthermore, hyperpigmentation occurs due to the DOPA reaction and melatonin enzymes such as Tyrosinase, Tyrosinase-Related Protein (TYRP1), and DOPA-chrome Tautomerase (TYRP2) during the skin graft healing process1–3. The overexpression of these enzymes can last for four weeks after the skin graft, leading to hyperpigmentation. The contraction process of the skin graft causes melanin accumulation and aggravates the degree of pigmentation.


Melanosomes in the skin grafted become more prominent, more pigmented, and resistant to lysosomes, leading to more severe pigmentation.4,5


Various medical treatments have been discovered to overcome hyperpigmentation by inhibiting tyrosinase activity. A skin-bleaching substance called hydroquinone is used to lighten dark skin patches brought on by hyperpigmentation, melasma, age spots, and freckles.6–10 For three months, it is applied topically to the hyperpigmented skin exclusively, twice daily, and many patients recover after that. Hydroquinone, however, may irritate the skin locally, resulting in post-inflammatory hyperpigmentation, which might exacerbate the skin pigmentation. Some researchers suggest using another anti-hyperpigmentation agent like kojic acid.11,12 Some researchers suggested using natural anti-tyrosinase such as Punica granatum flower. This flower exhibits great anti-tyrosinase activity in in-vitro using mushroom tyrosinase8,13; however, this plant is hard to find in Indonesia.

Kojic acid is a natural agent to lighten dark spots and even skin coloring brought on by melasma and post-inflammatory hyperpigmentation. The fermentation of rice wine and soy sauce also uses this molecule derived from mushrooms. In addition to having antibacterial, antimicrobial, and anti-inflammatory characteristics, kojic acid is a powerful antioxidant12. For three months, kojic acid is given topically to the hyperpigmented skin exclusively, twice daily, and many patients continue to improve after that time. It frequently works better when combined with other skin-lightening agents like hydroquinone.14,15 Although kojic acid is typically considered safe for health and beauty products, some may experience skin irritability, redness, and itching. It is significant to mention that those with sensitive skin or those allergic to mushrooms shouldn't take kojic acid.16,17


Coffee is a popular drink worldwide and especially abundant in Indonesia, the third largest country in green coffee robusta production. One of the best robusta coffee strains is BP-42, provided by the Indonesian Coffee and Cocoa Research Institute, Jember Regency, East Java. BP-42 coffee has the highest quality grain and a tremendous organoleptic score compared to other strains.18 It has a high caffeine and chlorogenic acid content.19–21 Caffeine has various benefits for health. People believed that caffeine from coffee could make skin healthy.22,23


Our previous study showed that Robusta BP-42 has the excellent potential of an anti-tyrosinase agent. BP-42 coffee extract has a high percentage of chlorogenic acid. We also found chlorogenic acid caffeine, trigonelline, palmitic acid, and hydroquinones to improve anti-tyrosinase activity. Chlorogenic acid found in Robusta BP-42 coffee, which is well known for its anti-inflammatory properties, may be an anti-hyperpigmentation treatment. According to the study, Jember's BP-42 coffee extract may be a contender for kojic acid, a component of cosmetics and anti-aging treatments.19 The study emphasizes the possible significant advantages of Robusta BP-42 coffee to reduce skin hyperpigmentation. Therefore, coffee may be a promising alternative to kojic acid for reducing hyperpigmentation after a skin graft surgery. However, the anti-hyperpigmentation activity of coffee extract compared to kojic acid is not well-known on grafted skin. This study compares the anti-hyperpigmentation activity of kojic acid and Robusta BP-42 coffee bean extract on skin-grafted rats.



Robusta Coffee BP-42 Extraction:

The Indonesian Coffee and Cocoa Research Institute has provided ground coffee beans of strain BP-42. This coffee bean meets the Indonesian Coffee and Cocoa Research Institute's inclusion requirements for being homogeneous and passing quality inspection. The maceration with 96% ethanol is used to extract the coffee bean.


Extract Gel Preparation:

Carbopol 2% and propylene glycol 15% were developed with distilled water. Then triethanolamine (TEA) 4% was added into the developed carbopol and propylene glycol. 27.6-gram gel was placed into the mortar, then added 5-gram dry extract of Robusta coffee beans was crushed homogeneously, and 100-gram coffee bean extract gel was obtained.


Preparing 1% kojic acid gel is the same principle as preparing Robusta coffee extract BP 42. When the gel base has been formed, 1 gram of kojic acid is added to 99 grams of gel to obtain a concentration of 1% kojic acid in 100 grams of gel.


Long Evans Rats:

Thirty-three male long Evans rats have been used as animal skin graft models. The dorsal skin of the rats is prepared for surgery. The skin was then disinfected with Betadine Veterinary Surgical and 70% alcohol. An excisional wound with a total diameter of 20 mm was made on the rat dorsum using a Humby knife. Split thickness wound was constructed above the fascia by taking a portion of the skin thickness.


The rats were anesthetized using 35.0 mg/kg Ketamine and 5.0 mg/kg Xylazine in the gluteal area. Once anesthetized, the hair in the dorsal region was carefully shaved. In this way, smooth and hairless skin grafts were obtained. The skin is disinfected and oiled with the help of fatty gauze. Desired length of graft was selected using a sterile marker. The width and thickness requirements of the graft are adjusted accordingly. With the non-dominant hand, the skin is glued to the bottom of the plate. Subsequently, the skin is ready for retrieval using a humby.


The donor wound will be the recipient of the cleaned skin graft. The wound was treated with gel. These rats were divided into three gel treatment groups: control negative (placebo gel), treatment group (5% robusta coffee BP-42 extract gel) and positive control (2% kojic acid gel). Wound care was carried out for 3-4 days. Antibiotics were administered for three days to prevent infection and death of the rats. During the study period, the animals were prevented from scratching, removing, eating, or licking the applied gel. We conducted the observation for 21 days. This study passed the ethical clearance from the University of Jember no 1657/UN25.8/KEPK/DL/2022.


Clinical Appearance Observation:

Rats were placed in well lighting room. Then, we took a picture of all the skin-grafted rats with a digital camera. The photos were taken on days 0, 4, 7, 11, 18 and 21 after the skin graft procedure. All the images were used to judge the level of pigmentation using ImageJ software. Image J software reads the skin's red, green and blue color (RGB). The higher value of ImageJ reading means more increased pigmentation occurred on the skin, and vice versa.


Histology observation:

Histological examination was performed on days 7, 14, 21 for all treatment groups. These histological preparations were stained with Masson Fontana. Pathologist experts scored the melanin granules and melanocytes on a histological sample.


Statistical Analysis:

The result was analyzed using mixed repeated-measures factorial ANOVA to observe the effect of dose and duration of the treatment.



Color Intensity of Long Evans Skin:


Figure 1. Average of skin color intensity after skin graft. NC: Negative Control, P: Treatment (5% Robusta BP-42 Coffee, PC: Positive Control (2% Kojic Acid)


Figure 1 showed the intensity of skin color on days 0 to 21 in the negative control group has the highest average compared to the positive control and treatment groups. The highest mean value in the negative control group occurred on the seventh day. In the treatment group, the average color intensity decreased from day four to day seven, followed by a slight increase from day 11 to day 18. Then, the average value fell on day 21. A similar condition occurred in the positive control group on days 4, 7 and 11. However, in the positive control group, color intensity decreased from day 14 to day 21.


Furthermore, statistical tests were carried out to see the differences between each treatment group using the two-way repeated measures ANOVA method with a confidence value of 0.05. The analysis of color intensity observations based on time showed that in the negative control group, there was a significant difference (p<0.05) between day seven and day 11. While in the positive control group, there was a significant difference (p<0.05) between day 14 and day 18. There was no significant difference in color intensity between the treatment group and the Robusta BP-42 coffee extract administration.


The analysis of color intensity observations based on treatment groups showed no significant differences on days 0, 4, 11, 14 and 18 in the three treatment groups. However, on days 7 and 21, there was a significant difference (p<0.05) in color intensity in the negative control group compared to the positive control and treatment groups. The treatment and positive control groups always showed results that were not significantly different on all days of observation. The results of this statistical analysis indicate that to cause the effect of changes in skin pigmentation, the interaction between treatment time and the dose is necessary. The longer the treatment time and the increase in the extract's dose will reduce the skin's pigmentation after the skin graft.


The camera used to take images of the skin after a skin graft has the principle of combining three different spectral bands: red, green, and blue (RGB). These color bands have significant overlapping values, thus creating redundancies. Melanin absorbs more light in the UV-blue part of the spectrum, so researchers look for melanin in the blue or use UV lighting.


Figure 2 Clinical appearance of long evans rats after undergoing skin grafts. NC: Negative Control, P: Treatment (5% Robusta BP-42 Coffee, PC: Positive Control (2% Kojic Acid)


Figure 2 shows that the condition of the skin graft on day 0 in all treatment types shows a dominant reddish clinical appearance compared to the color of the surrounding skin tissue. On day four, it was seen that all treatment groups had 100% skin graft take, but the wound condition in the negative control group was still reddish. Meanwhile, the appearance of red in the positive control and treatment skin grafts was minimal. On day 7, the negative control group showed the appearance of skin that was still reddish around the edges of the skin graft wound. In contrast, the reddish color had disappeared in the treatment and positive control groups, indicating that wound healing was faster and better than the negative control. On day 11, the skin graft of the negative control group still showed a reddish condition accompanied by protrusion around the wound edges. In the treatment and positive control groups, skin graft color resembled the surrounding skin with relatively flatter wound edges. It indicates no inflammation in the positive control group and the treatment group. On day 14, signs of inflammation in the wound of the negative control group had disappeared, and the color of the skin graft appeared darker than the surrounding skin.


Meanwhile, the positive control and treatment groups showed the same skin color as the surrounding skin color with better conditions. If the three treatment groups are compared, it shows that the state of the skin graft in the negative control has a darker color change than the treatment group and positive control. On day 18, grafted skin showed color changes in the three treatment groups were almost similar, where the brightness level of each group was the same as the surrounding skin. On day 21, grafted skin in the three groups was increasingly difficult to distinguish from the surrounding skin accompanied by dense hair.


Histological observations of the skin were observed three times, namely on days 7, 14 and 21 (Figure 3). The results showed that the negative control group had the highest number of melanin granules on the seventh day compared to the other groups. The positive control group had a slightly higher melanin granule score than the treatment group, but both groups had granule patterns of increase and decrease on the same day.


Figure 3: Observation of histological preparations of Long Evans rat skin after skin graft using Masson Fontana staining at 400x magnification.

NC: Negative Control, P: Treatment (5% Robusta BP-42 Coffee, PC: Positive Control (2% Kojic Acid). Arrow : Melanin Granule


Table 1: Friedman Test on Intraepithelial Granule Melanin by Time with Post Hoc using Wilcoxon Test





Day 7

Day 14

Day 21

Negative control










Positive control






We analyzed using the Friedman test to compare the scoring results between observation times. The analysis results (table 1) prove that the negative control and treatment have significantly different results on day 7 with days 14 and 21.

Table 2: Kruskal-Wallis Test on Melanocyte Cells Based on Treatment with Post Hoc using Mann-Whitney Test




Day  7

Day 14

Day 21

Negative control








Positive control









Kruskal-Wallis analysis was used to distinguish between treatments in one observation time. The study's results proved a significant difference (p<0.05) in the number of melanin granules between the negative control and positive control and treatment on day 21 (table 2).



The results show that robusta coffee extract BP-42 has an excellent clinical appearance and is similar to kojic acid as a positive control. Using Long Evans rats is the correct choice for testing skin pigmentation. This is in line with another study on hyperpigmentation that used a combination of 4% hydroquinone, 0.1% tretinoin, and 0.1% betamethasone mixed in cream and given to long Evans rats that had undergone skin grafts. The study results stated that the combination cream could reduce pigmentation. It explains that long Evans rats are an appropriate animal model for testing skin pigmentation.6


Robusta coffee extract BP-42 is applied topically in gel form. The choice of gel form is because the gel has the advantage of providing a cool, comfortable feeling and receiving a response from the external environment so that the release of active ingredients is controlled and can control the wound healing process. The gel was chosen because it is aqueous and can help reduce infection.24–26 The use of coffee extract gel has been proven in previous studies to help increase epithelial growth in the burn wound healing process and increase the number of osteoblasts and reduce osteoclasts in alveolar bone in the wound healing process of periodontitis rats.27


The similarity of clinical appearance in Long Evans rats and the ability of tyrosinase inhibition rate between positive control and Robusta coffee extract BP-42 indicates that coffee BP-42 can be used as a candidate for kojic acid replacement. Robusta coffee BP-42 has similar effectiveness to kojic acid because it has a variety of active compounds that support tyrosinase inhibition hydroquinone, free fatty acid, trigonelline, chlorogenic acid and caffeine.18,28–30


Chlorogenic acid is the dominant compound of robusta coffee extract BP-42 which has a vital role in reducing tyrosinase activity in skin graft wound healing compared to other anti-tyrosinase compounds. This result is supported by previous in-silico research. Chlorogenic acid could inhibit melanogenesis by binding to the active side of the tyrosinase enzyme. Tyrosinase enzyme turns into an inactive state. The binding energy of the active side of the tyrosinase enzyme by chlorogenic acid is -4.59kcal/mol. Conversely, the binding energy of kojic acid is -3.75 kcal/mol. The lower the binding energy of a compound, the greater the bonding strength of the compound.31,32


Chlorogenic acid acts not only as an anti-tyrosinase agent but also as an anti-inflammatory and antioxidant agent.33,34 Other studies mention that the presence of antioxidants plays an essential role in reducing pigmentation in the skin. Antioxidants can inhibit the process of pigmentation.4 This statement aligns with the observation of color intensity using Image J, which shows that only the negative control group experienced an increase in color intensity on the seventh day. The increase in color intensity occurs because the camera captures a reddish color on the mice's skin. It indicates there is still inflammation, while the treatment group using robusta coffee extract BP-42 shows no inflammation.35 High inflammation will affect the increase of pigmentation in the skin. Various inflammatory cytokine pathways (IL-4, IL-6, INF-ɣ, and TNF-α) can increase melanin production in melanocytes through the Microphthalmia-associated transcription factor (MITF) pathway.36,37


Caffeine is an active compound that is abundant in coffee. Caffeine has benefits as an anti-inflammatory agent and can stimulate the formation of angiogenesis and increase the production of extracellular matrix in the wound healing process through increased adenosine-receptor activity. This ability of caffeine has been shown to help accelerate grafted skin wound healing in Sprague Dawley rats.27,38 In silico research shows that the mechanism of tyrosinase inhibition by caffeine occurs due to the formation of a stable protein-ligand complex called the enzyme-caffeine complex. The presence of this complex causes inhibition of enzymatic reactions so that the melanogenesis process cannot enter the next stage.39


The free fatty acid is also an active substance that has the function of reducing inflammation. The free fatty acid has two compound derivatives: cafestol and kahweol.40 These two active compounds function synergistically with trigonelline to reduce inflammation. Trigonelline is a well-known compound for reducing inflammation. Other research states that trigonelline can reduce oxidative stress levels so that inflammation can decrease.41 Trigonelline is an appropriate compound for reducing inflammation due to the activity of hydroquinone. The decrease in the inflammatory process will reduce the stimulation of the mechanism of pigmentation formation after wound healing.4,42

Hydroquinone is a depigmenting compound that has become the gold standard. It is clinically used to treat areas of dyschromia, such as melasma, chloasma, solar lentigines, freckles, and post-inflammatory hyperpigmentation. The presence of hydroquinone in Robusta coffee extract BP 42 strengthens the reason that it can be used as a natural depigmentation agent. Recent research reported that hydroquinone, pyrocatechol, and 4-methyl catechol in coffee integrate to inhibit inflammatory activity against NF-kB through the Nrf2 activation pathway.43 This indicates that the hydroquinone content in coffee is relatively safer and does not increase inflammation in the skin.


Therefore, the results of this study indicate that Robusta BP42 coffee extract will be better used in future medication against hyperpigmentation. Robusta BP-42 coffee showed good clinical and histologic appearance compared to kojic acid and hydroquinone, which are said to have side effects in the form of inflammation characterized by redness of the skin and even cause cancer. It is because our coffee extract not only can inhibit the pigmentation process but also has other abilities possessed by Robusta coffee extract, such as anti-inflammatory, antioxidant, and antibacterial, which can reduce unwanted effects.


However, hemoglobin in blood vessels also absorbs in this region and needs to be considered in image analysis. Pigmentation can be evaluated in the red region, where melanin is the dominant chromophore. A formula can calculate the absorption index in the red channel based on the reflectance value. Image analysis software can convert RGB images to different color scales, providing quantitative information about skin color perception. However, hemoglobin or melanin concentration changes can affect all three color indices. Although this method is simple and inexpensive, color intensity measurements using RGB color bands are pretty accurate in describing pigmentation in the skin.35


Statistical results showed that time affected the multivariate test results with a value of p=0.000. The interaction between time and treatment also had a significance value of p<0.005. It means that a combination of time and therapy is needed to provide the effect of pigmentation changes. In this study, Levene's test was used to test the data's homogeneity, and the analysis results showed that the data were homogeneous at all treatment times.


The disadvantage of this ImageJ examination is that the color intensity captured by the system is influenced by many components on the surface of the skin graft, so residual blood, ointment residue, crusta and fine hair that grows can be a confounding factor in the analysis. Therefore, cleaning the skin graft surface and measuring the inch at each wound treatment is very important. In addition, repeated observations are needed to obtain consistent results.


Skin pigmentation can decrease because it is influenced by the dose and time of treatment of anti-tyrosinase contained in robusta coffee extract BP-42. Hydroquinone, a depigmentation compound found in robusta coffee extract BP-42 inhibits tyrosinase enzyme activity. Based on the study's results, it was found that to get optimal skin depigmentation, a higher dose of Robusta BP-42 coffee extract with more extended administration is needed.



Robusta BP-42 coffee extract from the Jember district has bioactive compounds related to skin graft pigmentation and is proven to have an antityrosinase effect. It results in pigmentation changes in clinical appearance and histologically in skin graft wounds.



The authors have no conflicts of interest regarding this investigation.



The authors thank Aditya Kurniawan, Candra Bumi and Rizky Januar Irvandi for their kind support during the statistical study and draft composting.



1.      Qian W, Liu W, Zhu D, et al. Natural skin‑whitening compounds for the treatment of melanogenesis (Review). Exp Ther Med.2020; 20: 173–185.

2.      D’Mello SAN, Finlay GJ, Baguley BC, et al. Signaling pathways in melanogenesis. Int J Mol Sci. 2016; 17: 1–18.

3.      Goswami-Giri A. Qualitative and Quantitative analysis of Dopa from Solanum melangena. Asian J Res Chem. 2014; 7: 954–963.

4.      Hossain MR, Ansary TM, Komine M, et al. Diversified stimuli‐induced inflammatory pathways cause skin pigmentation. Int J Mol Sci. 2021; 22.. DOI: 10.3390/ijms22083970.

5.      Videira IF dos S, Moura DFL, Magina S. Mechanisms regulating melanogenesis. An Bras Dermatol. 2013; 88: 76–83.

6.      Ozbey R, Okur MI. The use of 4% hydroquinone, 0.1% tretinoin, and 0.1% betamethasone creams to prevent hyperpigmentation of split-thickness skin grafts in Long-Evans rats. J Cosmet Dermatol. 2020; 19: 2663–2668.

7.      Nijhawan RI, Alexis AF. Practical approaches to medical and cosmetic dermatology in skin of color patients. Expert Rev Dermatol. 2011; 6: 175–187.

8.      Tan LF, Mogana R, Chinnappan S, et al. Various Plants and Bioactive Constituents for Pigmentation Control: A Review. Res J Pharm Technol. 2021; 14: 6106–6112.

9.      Goswami-Giri AS. Immobilized onion leaves tyrosinase on agar- Abelmoschus esculentus. Asian J Res Chem 2012; 5: 664–668.

10.   Duraisamy A, Narayanaswamy N, Balakrishnan K. Antioxidant and Anti-Tyrosinase Activity of Some Medicinal Plants. Res J Pharmacogn Phytochem. 2011; 3: 86–90.

11.   Muchtaridi M, Luthfika Dewi M. The recent update of deoxyarbutin: A skin depigmentation agent with tyrosinase inhibition targeting. Int J Appl Pharm. 2020; 12: 1–7.

12.   Phasha V, Senabe J, Ndzotoyi P, et al. Review on the Use of Kojic Acid—A Skin-Lightening Ingredient. Cosmetics. 2022; 9: 1–11.

13.   Gurale V V, D PM. Evaluation of Antioxidant and Tyrosinase Inhibitory Activity of Punica granatum Flower Extract. Res J Pharmacogn Phytochem. 2012; 4: 267–270.

14.   Kiattisin K, Nantarat T, Leelapornpisid P. Evaluation of antioxidant and anti-tyrosinase activities as well as stability of green and roasted coffee bean extracts from Coffea arabica and Coffea canephora grown in Thailand. J Pharmacogn Phyther. 2016; 8: 182–192.

15.   Migas P, Krauze-Baranowska M. The significance of arbutin and its derivatives in therapy and cosmetics. Phytochem Lett. 2015; 13: 35–40.

16.   Burnett CL, Bergfeld WF, Belsito D V., et al. Final report of the safety assessment of kojic acid as used in cosmetics. Int J Toxicol; 29. Epub ahead of print 2010. DOI: 10.1177/1091581810385956.

17.   Patel A. Postinflammatory hyperpigmentation: Review of pathogenesis, prevention, and treatment. Pigment Int 2014; 1: 59.

18.   Purwanto EH, Rubiyo, Towaha J. Karakteristik Mutu dan Citarasa Kopi Robusta Klon BP 42, BP 358 dan BP 308 Asal Bali dan Lampung. Sirinov, Balai Penelit Tanam Ind dan Penyegar. 2015; 3: 67–74.

19.   Elfiah U, Perdanakusuma DS, Saputro ID, et al. Robusta BP-42 coffee bean extract is a new anti-tyrosinase candidate to reduce melanogenesis activity. Bali Med J. 2022; 11: 2022–2026.

20.   Sari DS, Sakinah N, Nuri, et al. Chlorogenic Acid Fractionation in Robusta Green Bean Extract as a Combination Agent of Dental Pulp Stem Cells in Periodontal Tissue Engineering. Res J Pharm Technol. 2022; 15: 5005–5010.

21.   Deepthi BVP, Muthuprasanna P. Effect of Surfactant on Extraction of Caffeine from Coffee Powder. Res J Pharmacogn Phytochem. 2012; 4: 271–276.

22.   Roy A, Das B. Effects of caffeine on health: A review. Res J Pharm Technol 2015; 8: 1312–1319.

23.   Herman A, Herman AP. Caffeine’s Mechanisms of Action and Its Cosmetic Use. Skin Pharmacol Physiol. 2013; 26: 8–14.

24.   Ribeiro AS, Estanqueiro M, Oliveira MB, et al. Main benefits and applicability of plant extracts in skin care products. Cosmetics. 2015; 2: 48–65.

25.   Oakley A. Topical formulations, (2016, accessed 4 March 2023).

26.   Buhse L, Kolinski R, Westenberger B, et al. Topical drug classification. Int J Pharm. 2005; 295: 101–112.

27.   Prabowo WH, Awal Prasetyo, Neni Susilaningsih. The Effect of Multilevel Doses of Caffeine on Tissue Macrophage and Blood Lymphocyte Count in Autologous Full Thickness Skin Graft Healing in Sprague Dawley Rats. Biosci Med  J Biomed Transl Res; 6. Epub ahead of print 9 March 2022. DOI: 10.37275/bsm.v6i5.498.

28.   Charles-Bernard M, Kraehenbuehl K, Rytz A, et al. Interactions between volatile and nonvolatile coffee components. 1. Screening of nonvolatile components. J Agric Food Chem. 2005; 53: 4417–4425.

29.   Dong W, Tan L, Zhao J, et al. Characterization of fatty acid, amino acid and volatile compound compositions and bioactive components of seven coffee (Coffea robusta) cultivars grown in Hainan Province, China. Molecules 2015; 20: 16687–16708.

30.   Shivhare SC, Malviya KG, Malviya KKS, et al. A Review : Natural Skin Lighting and Nourishing Agents. Res J Top Cosmet Sci. 2012; 3: 11–15.

31.   Yudantara IMA, Cahyani NKN, Saputra MAW, et al. Chlorogenic acid and kojic acid as anti-hyperpigmentation: in silico study. Pharm Reports. 2022; 1: 23.

32.   Vijayakumar V, Radhakrishnan N, Vasantha-Srinivasan P. Molecular docking analysis of triazole analogues as inhibitors of human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and MMP 9) and tyrosinase. Res J Pharm Technol. 2020; 13: 2777–2783.

33.   Xu J-G, Hu Q-P, Liu Y. Antioxidant and DNA-Protective Activities of Chlorogenic Acid Isomers. J Agric Food Chem. 2012; 60: 11625–11630.

34.   Lin YL, Chang YY, Yang DJ, et al. Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters. Food Chem. 2013; 140: 31–38.

35.   Stamatas GN, Zmudzka BZ, Kollias N, et al. Non-invasive measurements of skin pigmentation in situ. Pigment Cell Res. 2004; 17: 618–626.

36.   Yamate Y, Hiramoto K, Sato EF. The Preventive Effect of Coffee Compounds on Dermatitis and Epidermal Pigmentation after Ultraviolet Irradiation in Mice. Skin Pharmacol Physiol. 2017; 30: 24–35.

37.   Huang HC, Wei CM, Siao JH, et al. Supercritical Fluid Extract of Spent Coffee Grounds Attenuates Melanogenesis through Downregulation of the PKA, PI3K/Akt, and MAPK Signaling Pathways. Evidence-based Complement Altern Med. 2016; 2016: 1–11.

38.   Ky CL, Louarn J, Dussert S, et al. Caffeine, trigonelline, chlorogenic acids and sucrose diversity in wild Coffea arabica L. and C. canephora P. accessions. Food Chem. 2001; 75: 223–230.

39.   Eun Lee K, Bharadwaj S, Yadava U, et al. Evaluation of caffeine as inhibitor against collagenase, elastase and tyrosinase using in silico and in vitro approach. J Enzyme Inhib Med Chem. 2019; 34: 927–936.

40.   Ren Y, Wang C, Xu J, et al. Cafestol and kahweol: A review on their bioactivities and pharmacological properties. Int J Mol Sci. 20. Epub ahead of print 2019. DOI: 10.3390/ijms20174238.

41.   Mohamadi N, Sharififar F, Pournamdari M, et al. A Review on Biosynthesis, Analytical Techniques, and Pharmacological Activities of Trigonelline as a Plant Alkaloid. J Diet Suppl. 2018; 15: 207–222.

42.   Fu C, Chen J, Lu J, et al. Roles of inflammation factors in melanogenesis (Review). Mol Med Rep. 2020; 21: 1421–1430.

43.   Funakoshi-Tago M, Matsutaka M, Hokimoto S, et al. Coffee ingredients, hydroquinone, pyrocatechol, and 4-ethylcatechol exhibit anti-inflammatory activity through inhibiting NF-κB and activating Nrf2. J Funct Foods. 2022; 90: 104980.






Received on 15.04.2023            Modified on 22.05.2023

Accepted on 14.06.2023           © RJPT All right reserved

Research J. Pharm. and Tech 2024; 17(2):636-642.

DOI: 10.52711/0974-360X.2024.00099