1. INTRODUCTION:

Acne, also known as acne vulgaris, is a chronic inflammatory skin disease involving the sebaceous glands. It is characterized by papules, pustules, nodules, cysts, and scarring, often accompanied by seborrhea. Acne occurs when hair follicles are clogged with dead skin cells and oil from the skin that forms a bump on the skin, called comedones.^{1, 2}

Acne can occur at all ages; however, it is the most common skin disease in the age group of 12 to 24 years, affecting about 80% of teenagers and young adults.² According to the Global Burden of Disease Study 2019, acne is the eighth most common skin disease, with an estimated global prevalence of 9.4% for all ages.³ Over the last decade and a half, the prevalence has increased by around 5%.⁴

Multiple etiological factors are involved in the development of acne. Four key pathological processes include i) androgen-induced increased sebum hyperproduction, ii) altered follicular keratinization that leads to comedones, iii) colonization and proliferation of duct by Propionibacterium acnes, and iv) complex inflammatory process involving both innate and acquired immunity.^4,
5 Genetics, diet, environmental pollution, social environment, and lifestyle are the etiological factors that contribute to the pathogenesis of acne.^{4, 5}

Several studies have found that acne adversely affects the social life, self-esteem, appearance, and quality of life of individuals. Moreover, acne is often co-morbid with mental disorders, including depression and anxiety. It is associated with substantial financial costs.^{2, 4}

Bakuchiol is a meroterpene phenol and a principal bioactive component present in seeds and leaves of the species Cullen corylifolium (Psoralea corylifolia).^{6, 7}Since its discovery in 1966, it has been reported to possess a broad range of biological and pharmacological properties.⁸ Bakuchiol has gained popularity as an active ingredient in cosmetic skincare products due to its retinol-like functionality and efficacy but better safety than retinoic acid.³

In many studies, Bakuchiol has shown promising effects as a monotherapy as well as a complementary therapy with currently available formulations in the treatment of facial acne. This study was conducted to evaluate the safety and efficacy of Bakutrol™, a topical formulation composed of P. corylifolia containing 0.5% bakuchiol, in patients with facial acne.

2. MATERIAL AND METHODS:

2.1 Study design:

This was a prospective, open-label, single-arm study. The study was conducted from August 2022 to November 2022. Institutional Ethics Committee approved the study (Protocol number: RRS/CL/AAC/ 2022 Dated: 21/07/2022) and was registered in Clinical Trials Registry- India (CTRI registration no: CTRI/2022/08/044766 Dated: 2/08/2022). The study was conducted as per the clinical research guidelines established by the Supplements and Cosmetics Act, 1940 of India, Supplements and Cosmetics Rules, 1945 of India, Ethical Guidelines for Biomedical Research on Human Participants, 2006 of Indian Council of Medical Research (ICMR) in India, the principles enunciated in the Declaration of Helsinki and the ICH-harmonized tripartite guideline regarding Good Clinical Practice (GCP). All patients provided written, informed consent to participate in the study prior to being screened.

2.2 Subjects:

The study was planned with a total of 50 participants. Male and female patients aged 18 to 35 years were included in the study. The key inclusion criteria were diagnosis of moderate facial acne vulgaris, phototype I, II, III, or IV according to Fitzpatrick classification, facial inflammatory lesion count >20, non-inflammatory lesions count of at least 20-100, and Investigator’s Global Assessment score of 3.

Patients were excluded from the study if they had two nodulocystic lesions, prior topical acne treatment, or systemic anti-inflammatory agents in the past 14 days. Other key exclusion criteria were the use of systemic corticosteroids, antibacterial, immunosuppressant drugs, or abradant facial procedures in the past 30 days, the presence of other concurrent facial skin diseases, and patients who are photosensitive or who are likely to engage in activities that involve excessive or prolonged exposure to sunlight, patients with drug-induced acne, with menopausal disorders, had a history of significant reactions to topical acne treatments, or a known allergy or hypersensitivity to any listed ingredients and use of oral retinoid within six months of baseline visit.

2.3 Interventional agent and treatment:

Bakutrol^TM (a registered trademark of Unigen Inc. USA), is a standardized natural skin conditioning agent that contains 0.5% bakuchoi. It is derived from the plant Psolarea corylifolia. Bakuchoi, an active component of the plant is extracted using a proprietary process that eliminates toxic coumarin contamination.

The participants were instructed to gently apply Bakutrol^TM cream containing 0.5% bakuchiol as a thin layer over the acne lesions twice daily after washing the face with a gentle cleanser and dabbing it dry with a clean towel. A moisturizer or sunscreen was allowed to be used by the participants as and when required. The total duration of the study was 60 days. The first visit was planned on day 0 to evaluate the baseline parameters. Later visits were scheduled biweekly- on days 15, 30, 45, and 60.

2.4 Primary and secondary endpoints:

The primary outcomes evaluated were the safety of Bakutrol^TM in patients with facial acne and its efficacy in controlling P. acnes infection in these patients. The anti-inflammatory effect was the secondary outcome evaluated in the study. Inflammatory lesions, such as papules, pustules, or nodules, were captured through video-dermoscopy and photographic images with the DermaLab Combo-Cortex Technology instrument to record the anti-inflammatory effect of the treatment visually. The treatment effect was also assessed through the IGA (Investigators Global Assessment) considering the quality and quantity of the acne lesions (IGA scale: moderate = 3, mild = 2, almost clear = 1, clear = 0). Table 1 summarizes the parameters assessed during each visit.

Table 1: Parameters Evaluated During the Study Period

Activity	Baseline Day 0	Day 15	Day 30	Day 45	Day 60
Demographics and vital signs	√	-	-	-	√
General physical examination	√	-	-	-	√
Dermatological Assessment	√	√	√	√	√
Video-dermoscopy	√	√	√	√	√
Photographic Images	√	√	√	√	√
Acne-specific microbiome analysis	√	√	√	√	√
Subject Self-assessment	√	√	√	√	√
Adverse event monitoring	√	√	√	√	√

2.5 Statistical analysis:

Descriptive statistical analysis was carried out in this study. For normally distributed data, parametric tests were applied, results on continuous measurements were presented as Mean ± SD, and results on categorical measures were presented in significance level. A statistical significance of < 0.05 was considered significant. Student t-test (paired) was employed to find the significance of the change from baseline (day 0) to day 60 subjective assessments—repeated measures ANOVA was used to find the overall significance for the above measurements. Percentage changes for categorical data were assessed from Day 0 to Day 60.

3. RESULTS:

3.1 Demographics and other baseline characteristics:

All 50 enrolled participants completed the study. The demographic characteristics of the participants at baseline are given in Table 2.

Table 2: Demographic characteristics of the study participants

Characteristics
Total Participants (N)	50
Male	15
Female	35
Mean age (years)	28.02
Mean weight (Kg)	61.20
Mean height (cm)	160.00
Mean BMI (kg/m²)	23.86

Vitals parameters like temperature, heart rate, pulse rate, respiratory rate, and systolic and diastolic blood pressure were found to be normal for all the study subjects.

None of the subjects received any other concomitant medications during their study period.

3.2 Primary outcomes:

3.2.1 Assessment of Safety Parameters:

Physical examination parameters like general appearance, ENT, heart, lungs, abdomen, extremities, and neurological parameters were normal for all the study participants during the study period.

Medical history showed that ENT, cardiovascular, respiratory, endocrine, gastrointestinal, hepatobiliary, genitourinary, musculoskeletal, neurological, psychological, hematological, immunological, dermatological, allergies, and other conditions were not seen in any of the study participants.

Figure 1 Shows gradual reduction (%) in bacterial load (P. acnes) during the treatment period.

3.2.2 Assessment of Efficacy Parameters:

Microbiome Analysis:

Microbiome analysis showed a clinically meaningful reduction in P. acnes bacterial load at the end of the study. Outcomes are presented in Figure 1.

As shown in fig 1, there was gradual reduction of bacterial load (P. acnes) from the baseline value. On day 15, the bacterial load reduced by 16.71%, and continuously reduced there after by 26.51%, 31.66% 46.14 % by 30, 45 and 60 days of treatment respectively.

3.3 Secondary outcomes:

3.3.1 Video-dermoscopic and photographic analysis:

Video-dermoscopic results showed that treatment with Bakutrol^TM cream significantly reduced inflammatory and non-inflammatory acne lesions by day 30 and cleared lesions by day 60 (Figure 2).

Figure 2 Shows a representative video-dermoscopy results showing decrease in acne lesions by day 60 of treatment.

Figure 3: Representative photographic images of a male and a female patient before and after the treatment with Bakutrol^TM.

3.3.2 Investigators Global Assessment⁹:

Bakutrol^TM treatment for 60 days was found to be effective reducing both inflammatory and non-inflammatory. Ten out of 50 patients (2 from group 1 and 8 from group 2) completely cleared acne (20%) with IGA score ‘0’. The remaining 40 patients (80%) showed a reduction in IGA score over their baseline value to mild (Score 2) to almost cleared acne (Score 1). Figure 3 shows photographic demonstration of acne clearance at the end of the treatment with Bakutrol^TM.

The severity of acne was assessed on all 50 patients using the IGA method. Based on the baseline IGA score patients were divided into 2 groups. Out of 50 patients 33 (66%) had IGA score 3 (Group 1) and 17 (34%) had IGA score 2 (Group 2) at the base line. Patients when treated with Bakutrol^TM, in group 1 patients, IGA score reduced from 3 to 2 in 13 patients (19.7%), to 1 in 18 patients (27%). The remaining 2 patients cleared their acne completely with ‘0’ IGA Score. Similarly in the group 2 patients (n= 17), IGA score reduced from 2 to 1 in 9 patients (53%). The remaining 8 patients (47%) cleared achene at the end of treatment. (Fig 4).

Fig. 4. IGA Score before and aftger treatment with Bakutrol

Figure 4 shows number of patients (y-axis) showing Investigator’s Global Assessment (IGA) score as assessed by quality and quantity of acne lesions (IGA scale: moderate = 3, mild = 2, almost clear = 1, clear = 0 indicated by colour bars). Patients were divided into two groups based on their baseline IGA score as Group 1: n=33 with score 3 and group 2: n=17 with score 2). Remaining bars in each group show the number of patients with their respective score at the end of the treatment.

4. DISCUSSION:

Acne remains one of the most disturbing skin conditions that adversely affect individual daily life. The four pathogenic processes discussed earlier, including excessive sebum production, follicular hyper keratinization, bacterial colonization by P. acnes, and inflammation, are the major targets for acne therapy.¹⁰

Currently, oral or topical retinoic acid is the only single agent effective against all four targets of acne therapy. However, at a therapeutic dose, retinoic acid is responsible for several serious side effects. Hence, its use is suggested only in the most severe cases, and alternative treatment approaches should be considered first.^1,11 The most common alternate approaches to retinoic acid include exfoliating agents such as salicylic and glycolic acid, but these agents make the skin more sensitive to sun-induced damage when used for long periods of time. ¹

Bakuchiol is a plant-derived meroterpene extracted from the edible seeds of Psoralea corylifolia. Studies have demonstrated its effectiveness against the four primary pathophysiological mechanisms responsible for the development of acne. Moreover, Bakuchiol has the potential to synergize with existing anti-acne agents and augment their therapeutic efficacy. ¹

The different properties of active ingredients in dermo-cosmetics for acne may include sebum-controlling, antimicrobial, anti-inflammatory, antioxidant, and/or keratolytic.¹² In studies evaluating Bakuchiol for its effects on photoaging, acne, and post-inflammatory hyperpigmentation (PIH), topical Bakuchiol has demonstrated comparable or even better beneficial effects to those achieved by topical retinoids. ^{13, 14} Current evidence suggests that Bakuchiol is likely the only agent after retinoic acid shown to be effective against multiple pathways involved in the pathogenesis of acne.^{1, 15}

Acne is mainly triggered by P. acnes under the influence of normal circulating dehydroepiandrosterone (DHEA).¹⁶ P. acnes has proinflammatory characteristics exceeding that of both Streptococcus and Staphylococcus strains. It plays a role in the induction and distribution of inflammation in the pilosebaceous follicle. P. acnes also targets and damages keratinocytes as well as sebocytes.¹⁷ Studies have also indicated excellent P. acnes inhibitory activity of Bakuchiol. It is also very effective in inhibiting other microbiomes on the surface of the stratum corneum, such as Staphylococcus and Candida.¹ In our study, microbiome analysis showed that the application of Bakutrol™ face cream resulted in a clinically meaningful reduction in P. acnes bacterial load.

Facial acne can present with inflammatory lesions (papules, pustules, and nodules), non-inflammatory lesions (open and closed comedones), or a mixture of both and varying degrees of scarring.^{5, 16} The ability of Bakuchiol to modulate levels of inflammatory mediators makes it an appealing option for the treatment of acne.¹⁵ Bakuchiol has moderate inhibitory activity against COX-2 and a strong inhibitory activity against COX-1.²¹ In addition; Bakuchiol has demonstrated inducible NO synthase (iNOS) inhibitory activity. ¹⁸ Interestingly, retinol was not found to inhibit iNOS.¹⁹ Studies have found that Bakuchiol also has anti-neuroinflammatory effects.²⁰ Bakuchiol has a strong antioxidant action via a radical scavenging activity which is also higher than retinol.^{13, 21} In this study, Bakutrol™ face cream showed a clinically meaningful reduction in inflammatory lesions at the end of the study.

Dihydrotestosterone (DHT) is a key driver of the overproduction of sebum and proinflammatory cytokines in acne. Like retinoic acid, Bakuchiol also down-regulates the conversion of testosterone to DHA by down-regulating the formation of 5-α-reductase.^1,
22 Bakuchiol has several biopositive effects, like the stimulation of the critical extracellular matrix component fibronectin and accelerated epidermal regeneration and wound healing not seen with retinoic acid.¹³

A recent clinical study by Brownell et al. showed that monotherapy with topical bakuchiol cream on facial acne improves mild to moderate acne.²³ The topical application of Bakuchiol significantly reduced the number of inflammatory lesions and improved existing acne-related post-inflammatory hyperpigmentation. It may be particularly well suited for individuals with colored skin. In another clinical trial by Polakova et al., the bakuchiol Ginkgo biloba extract and mannitol complex were found to improve the treatment outcomes of Adapalene gel in acne patients with significant improvement in the inflammatory and non-inflammatory lesions, Investigator Global Assessment, global efficacy, and seborrhea intensity.

Bakuchiol also has multidirectional efficacy against cellular hallmarks of skin aging.¹³²⁰ A study comparing Bakuchiol with retinol showed that Bakuchiol has a comparable ability to improve facial photoaging.²⁴ Bakuchiol significantly improves various cutaneous parameters, such as lines, wrinkles, pigmentation, elasticity, and firmness. Additionally, it reduces photodamage effectively without causing the undesirable side effects that are commonly associated with retinol therapy.²⁵

Topical Bakuchiol was cosmetically acceptable and well-tolerated in patients with acne.²³ The topical Bakuchiol was also well tolerated in individuals with sensitive skin. Topical bakuchiol is a more tolerable alternative to retinol.^{15, 24} In the current study, Bakutrol™ cream demonstrated excellent safety outcomes complementing the earlier evidence, due to which it can be used at any time of the day.

5. CONCLUSION:

Bakutrol™ face cream is safe and effective in the treatment of facial acne. The outcomes of this study and earlier evidence are suggestive of the rationale for the use of Bakuchiol in the treatment of facial acne. The study supports the use of Bakutrol™ face cream as a safe and natural skin care product active against acne.

6. CONFLICT OF INTEREST:

None

7. ABBREVIATIONS:

COX	Cyclooxygenase
CTRI	Clinical Tral Registry- India
DHA	Docosa Hexaenoic Acid
DHT	Dihydrotestosterone
ENT	Ear Nose Throat
GCP	Good Clinical Practice
ICH	International Council for Harmonization
ICMR	Indian Council of Medical Research
IGA	Investigator’s Global Assessment
iNOS	Inducible Nitric Oxide synthase
NO	Nitric Oxide

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Received on 10.10.2024 Revised on 07.12.2024

Accepted on 19.01.2025 Published on 28.03.2025

Available online from April 01, 2025

Research J. Topical and Cosmetic Sci. 2025; 16(1):33-38.

DOI: 10.52711/2321-5844.2025.00006

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.