Gotu Kola (Centella asiatica)

Airline passengers experience a range of symptoms when travelling on long flights. This review evaluated the efficacy of functional foods, beverages, and supplements claiming to address the effects of air travel for healthy adults. Products were identified in a scoping review of electronic databases, search engines, and grey literature (March to August 2019). A systematic review of the efficacy of product ingredients was conducted using five electronic databases from inception to February 2021. Articles were screened, data extracted, and assessed for risk of bias by two researchers independently. Meta-analysis was performed. Of the 3842 studies identified, 23 met selection criteria: melatonin (n = 10), Pycnogenol (n = 4), various macronutrients (n = 2), caffeine (n = 2), Centella asiatica (n = 1), elderberry (n = 1), Echinacea (n = 1), fluid (n = 1), and Pinokinase (n = 1). Meta-analysis (random effects model) indicated melatonin reduced self-reported jetlag following eastbound (n = 5) and westbound (n = 4) flights: standard mean difference -0.76 (95% CI = -1.06 to -0.45, I2 0%, p < 0.00001) and -0.66 (95% CI = -1.07 to -0.26, I2 45%, p = 0.001), respectively. Pycnogenol also reduced edema scores (n = 3), standard mean -4.09 (95% CI = -6.44 to -1.74), I2 98%, p = 0.0006). Overall, 12 of 183 ingredients contained in 199 products had evidence to support claims.

Centella asiatica (L.) Urb. has been used as an herbal brain tonic for mental disorders and enhancing memory, but no review of the overall evidence of C. asiatica and cognitive function has been conducted. This study aims to determine the effects of C. asiatica on cognitive function and its related properties. The current systematic review includes five randomized controlled trials (RCTs) conducted to determine the effect of C. asiatica alone and six RCTs conducted to determine the effect of C. asiatica-containing products. Meta-analysis indicated that there are no significant differences in all cognitive function domains of C. asiatica when compared to placebo. However, it could improve mood by increasing alert scores [SMD: 0.71 (95% CI; 0.01 to 1.41); I2 = 30.5%] and decreasing anger scores at 1 hour after treatment [SMD: -0.81 (95%CI; -1.51 to -0.09); I2 = 36.6%]. None of the studies reported adverse effects of C. asiatica. In conclusion, there is not strong evidence to support the use of C. asiatica for cognitive function improvement in each cognitive domain. C. asiatica could improve alertness and relieve anger. However, some limitations should be aware including dose regimen, plant preparation, standardization, and product variation. Future well-designed clinical trials using suitable doses of standardized C. asiatica are still needed.

Background/Objectives: Macular pigment optical density (MPOD) is a nutrition-responsive biomarker that indicates the antioxidant status of the macula. This study aimed to evaluate the effects of long-term supplementation with a standardized Centella asiatica (L.) Urb. extract (CA-HE50) on MPOD in a randomized, double-blind, placebo-controlled clinical trial. Methods: Eighty men and women aged 45-65 years, with baseline MPOD values between 0.2 and 0.4, were randomly assigned to receive either CA-HE50 (300 mg/day, n = 40) or a placebo (n = 40) for 6 months. Efficacy was assessed by measuring MPOD at baseline and on Days 60, 120, and 180. The primary efficacy endpoint was the change in MPOD from baseline to Day 180. Safety was evaluated through monitoring adverse events, vital signs, and clinical laboratory tests. Results: By Day 180, supplementation with CA-HE50 resulted in a statistically significant increase in MPOD compared to the placebo in the right eye, left eye, and the average of both eyes (all p < 0.001). Significant between-group differences were also observed at Day 120, indicating a time-dependent improvement in MPOD. Additionally, the proportion of responders was significantly higher in the CA-HE50 group compared to the placebo group (p < 0.001). CA-HE50 was well tolerated, with no serious adverse events or clinically relevant safety concerns identified during the intervention period. Conclusions: Long-term supplementation with C. asiatica extract significantly improved MPOD, supporting its potential role in enhancing macular nutritional status. These findings suggest that CA-HE50 may serve as a beneficial dietary intervention for maintaining macular health.

BACKGROUND: Facial laser procedures may result in compromised skin barrier function and associated discomfort. It is essential to address these issues to facilitate a swift recovery and enhance patient satisfaction. OBJECTIVE: To evaluate the efficacy and safety of a panthenol-enriched mask, incorporating centella asiatica extract (madecassoside) and bisabolol, in repairing the skin barrier after 1550 and 1927 nm dual-wavelength non-ablative fractional laser therapy. METHODS: A total of 60 subjects were enrolled in this double-blind randomized study and were divided into Control group (CG) and Mask group (MG). Both groups received standard post-operative care, the MG receiving the Mask, while the CG received a saline dressing. Skin barrier repair was assessed using a skin physiological detection instrument, colorimetry, and a skin imaging analyzer (VISIA). The incidence of adverse reactions was also monitored. RESULTS: The MG exhibited significantly lower erythema index and hyperpigmentation index at D3, D7, and D14, compared to the CG. The MG had significantly higher sebum content than the CG at D7 and D14. The stratum corneum moisture content in the MG was also higher than in the CG at D3, D7, and D14. Additionally, transepidermal water loss (TEWL) was significantly reduced in the MG at D3, D7, and D14. There was no significant difference in the rate of adverse reactions between the groups. CONCLUSION: A panthenol-enriched Mask effectively decreased post non-ablative laser erythema, enhanced skin hydration, and promoted skin barrier repair. © 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

OBJECTIVE: To determine the efficacy of Centella asiatica extract, ECa233, on alleviating pain symptoms and functional improvement of acute temporomandibular disorders (TMD). MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, pilot clinical trial was performed using 23 adults with acute TMD. They were randomly assigned into four treatment groups, an ibuprofen (positive control) group, two test groups of ECa233 each of 250 mg, and 500 mg extracts, and a placebo (negative control) group. All subjects were requested to self-administer the test/control capsules, twice a day for 14 days. The pain intensity score, range of mandibular motion and tenderness of the masticatory muscles and temporomandibular joint (TMJ) were recorded at baseline, 7- and 14-days post-treatment. RESULTS: One week after intervention, the pain intensity score significantly decreased in participants receiving 500 mg of ECa233 (P = 0.016), as well as the placebo group (P = 0.030) but not in the other groups. Additionally, those receiving 500 mg of ECa233 displayed the highest percentage reduction in self-reported pain intensity and pain on TMJ palpation compared with the other groups (P > 0.050). On day 14, there were no significant differences observed among the evaluated parameters in the four groups. CONCLUSIONS: The orally administered ECa233 has the potential to induce rapid, short term, dose-dependent analgesia in individuals with TMD pain. However, longer-term RCT with a larger cohort is necessary to confirm these findings. CLINICAL RELEVANCE: ECa 233 at 500 mg has the potential to induce a more rapid analgesic response in individuals with acute TMD after a 7-day period. TRIAL REGISTRATION: This trial was registered on the ClinicalTrials.gov, the number is NCT06231212, date of registration: 30/01/2024. © 2025. The Author(s).

BACKGROUND: There is increasing recognition of dermatoporosis - a condition of chronic cutaneous fragility of aging skin seen primarily in older adults. Dermatoporosis can be characterized by white pseudo scars, purpura/bruising, skin thinning, and loss of volume. This study evaluated a novel cream with microdoses of mandelic acid and Centella asiatica that was formulated to target physiologic processes involved in dermatoporosis. METHODS: A 12-week, proof-of-concept study of participants aged 65 years and older (n=54) with sensitive skin and dermatoporosis managed with twice-daily application of the cream on both forearms and 1 leg (randomly selected, with the other leg serving as control). Key assessments included transepidermal water loss (TEWL), skin thickness measurement by ultrasound, clinical scoring for dryness and roughness, a participant questionnaire, and standard safety assessments. RESULTS: Twice-daily use of the novel cream resulted in an ongoing consistent positive increase in skin thickness of 5% (P&lt;0.05), with improvements primarily in the dermis and epidermis but also notable in the subdermal layer. Significant improvements in hydration were observed starting from Day 7 and observed through Day 84 (or end of study) (P&lt;0.05). Changes in TEWL showed a 20% improvement in barrier function that also was apparent early (Day 7) and sustained through the study (40% improvement at day 84, P&lt;0.05). The cream demonstrated excellent safety with no adverse reactions and no worsening in tolerability parameters. CONCLUSIONS: This cream, containing microdoses of mandelic acid and Centella asiatica, safely and effectively improved skin thickness, firmness, and resiliency, and had high acceptability with study participants. J Drugs Dermatol. 2025;24(4):352-356. doi:10.36849/JDD.8947.

Aim of study is to analyze Bromelain' effects on the most common early complications after BCS (oedema and seroma). From January 2021 to December 2023 a double-blind randomized placebo-controlled trial was performed on 114 candidates for BCS at our Academic Unit. Group A received a supplement of Casperome™-Boswellia Phytosome® + Bromelain (CBB) in combination with alpha-lipoic acid + superoxide dismutase + B and D vitamins + centella asiatica. Group B received a supplement of CBB + placebo. Group C received placebo. The therapies were administrated for 30 days. On GEE logistic regression, drugs combination in A seems to be associated with statistical fewer oedema compared with C (P = 0.018 at 1 day and P = 0.002 after 1 month). Comparing B to C, B gained a significative value after 1 month (P = 0.007). On GEE logistic regression, the drugs combination in A has been associated with statistical fewer seroma compared with C (P = 0.009 at 15thpostoperative day and P < 0.001 after 1 month). B vs C reaches significant values 15 day and 1 month after surgery (P = 0.002 and P < 0.001, respectively). The current study is the first analyzing the employment of CBB association with/without neurotrophic agent on prevention of early complications after BCS. © 2025. The Author(s).

BACKGROUND: Mohs micrographic surgery is the gold standard treatment for skin cancers in cosmetically sensitive anatomic areas, with a cure rate close to 100%. Managing post-Mohs surgery wounds can pose challenges, particularly in elderly patients. This study evaluates the Cicaglocal drug, a supplement with bromelain, Centella asiatica, hyaluronan, vitamins, and minerals, for enhancing wound healing post-Mohs surgery. METHOD: This double-blinded, randomized clinical trial conducted at Al-Zahra Hospital in 2023 involved 24 patients aged 50-80 with SCC or BCC undergoing Mohs surgery. Patients were randomized into two groups Cicaglocal and placebo. Treatments were administered postoperatively, and outcomes such as erythema reduction, early healing score (EHS), full recovery, and patient and physician satisfaction levels were evaluated 7 and 14 days after initiation. Data were collected through clinical assessments and standardized wound photographs. RESULT: Oral Cicaglocal demonstrated significantly improved outcomes compared to their respective placebo groups in terms of erythema score, EHS, full recovery score, and patient and physician satisfaction levels. CONCLUSION: Cicaglocal can enhance wound healing and lead to improved clinical outcomes following Mohs micrographic surgery. © 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

A randomised open clinical/laboratory study was performed to evaluate the safety and cosmetic efficacy of facial cosmetics for females during the menopausal period. The cosmetics contain active ingredients of meristem cells derived from the medicinal plants Leontopodium alpinum, Buddeleja davidii, Centella asiatica, and Echinacea angustifolia. Recently, the major bioactive molecules of these medicinal plants (leontopodic acid, verbascoside, asiaticoside, and echinacoside, respectively) have been thoroughly evaluated in vitro for molecular pathways and cellular mechanisms and their preventive/curative effects on human skin cells exposed to factors promoting premature skin ageing and cellular senescence. Nevertheless, clinical data on their safety/efficacy to ageing human skin are scarce. This clinical study enrolled 104 Caucasian females in pre-menopause, menopause, or post-menopause periods. They applied cosmetic serums daily for 1 month. Questionnaires and instrumental and biochemical methods were used to assess dermatological/ophthalmological safety and cosmetic efficacy through changes of the skin physiology markers characteristic of ageing/menopause (elasticity, barrier functions, moisture, sebum, ultrasonic properties, and collagen content and structure). Quantitative microbiological tests were carried out for skin microbiota fluctuations. Data showed that the cosmetics were safe, and they shifted the skin physiology parameters to a younger biological age, enhanced collagen synthesis, inhibited lipid peroxidation, and favoured normal microbiota.

OBJECTIVE: To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea. METHODS: Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score. RESULTS: A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants. CONCLUSION: The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use. © 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

OBJECTIVE: To study the clinical efficacy of a polymeric spray film containing Centella asiatica extract to heal acute wounds. METHOD: A polymeric spray film solution for wound healing was formulated using Centella asiatica extract, which contained triterpenes, including asiatic acid, madecassic acid, asiaticoside and madecassoside. The stability and physicochemical properties of the formulation were evaluated, and a multicentre, randomised, controlled trial was conducted to assess its clinical wound-healing efficacy. The Pressure Ulcer Scale for Healing (PUSH Tool) score was used to evaluate wound healing on days 0, 3, 5 and 7. RESULTS: The cohort consisted of 60 volunteers with clean-contaminated wounds (class 1), randomly assigned to the Control (n=30) and Testing (n=30) groups. The spray product contained asiatic acid, madecassic acid, asiaticoside and madecassoside at 0.20±0.02mg/ml, 0.16±0.01mg/ml, 0.32±0.03mg/ml and 0.10±0.00mg/ml, respectively. The pH value was 5.5±0.01, and the viscosity was 33±4cP. The product was stable for six months when stored at 30±2°C and at 40±2°C, in 75±5% relative humidity. The tested product significantly reduced the total PUSH and exudate scores, indicating that the polymeric spray film solution containing Centella asiatica improved wound healing. The average healing recovery times for the Testing and Control groups were 4.6±1.1 days and 4.87±1.0 days, respectively. CONCLUSION: In this study, Centella asiatica extract-containing polymeric spray film solution was beneficial as an acute wound medication, which could shorten healing time with no adverse effects.

The present study aimed to optimize a multi-herbal combination exerting the greatest antioxidant property using statistical method for anti-skin aging application as well as to elucidate its in vivo safety and anti-skin aging potential. The multi-herbal combination was optimized using a two-level, full factorial approach by exploring the correlation between the concentrations (0-3%w/v) of three extracts from Centella asiatica (CA), Momordica cochinchinensis (MA), Phyllanthus emblica (EM). An anti-skin aging emulsion containing the optimized combination was then developed and evaluated for its physicochemical characteristics with its stability under storage conditions. The in vivo anti-skin aging potential of the emulsion was subsequently investigated among 60 women in a randomized, double-blind, placebo-controlled study. Skin hydration, elasticity and wrinkles at eye and cheek areas were measured at baseline, after 30 and 60 days of application. Before performance testing, in vivo skin irritation was evaluated using the patch test and homogeneity between groups was also statistically analyzed. According to the model describing the significant main effects of each extract and interaction effects between extracts on percent inhibition against DPPH radicals, the best multi-herbal combination consisted of 3%w/v EM and 3%w/v CA. The developed emulsion containing the combination presented smooth soft texture with good stability in terms of physical characteristics and biological property. Regarding the clinical study, no skin erythema and edema was reported among in all volunteers. After 60 days of application, significantly improved skin hydration, elasticity and wrinkles were observed in the test group. In addition, significantly reduced wrinkles were observed after 60 days in both skin areas of the test group. The anti-skin aging emulsion containing this optimized combination exhibited good safety and performance. Ultimately, this product comprises an effective anti-skin aging formulation for applications. © 2023. The Author(s).

INTRODUCTION: One of the biggest challenges associated with tuberculosis is the emerging drug resistance which emphasizes the need of alternative therapeutic approaches. In recent years, multitargeting approach for TB therapy has garnered considerable attention. The Antigen85 complex of proteins represent key enzymes which are involved in Mtb cell wall biosynthesis. This study aims at investigating the antimycobacterial effects of Centella asiatica and its two compounds - asiatic acid and quercetin against these three proteins and validate them as multi targets for drug targeting. METHODS: Three-fold validation approach included in-silico studies, in-vitro inhibitory studies against MtbH37Ra strain and inhibition studies against recombinant enzymes. RESULTS: Displaying good bioavailability, asiatic acid and quercetin exhibited favorable binding affinities. Disruption of the integrity of the cell membrane of MtbH37Ra was observed through electron microscopy and flow cytometry. Both compounds and extract showed inhibitory activity against the enzymes and microorganism and were found to act synergistically in conjunction with isoniazid. Asiatic acid demonstrated bactericidal activity. The reduced reaction rate of the recombinant enzymes implied their function and activity were hampered, which was confirmed through a fluorometric assay. CONCLUSION: These results highlight the potential of asiatic acid and quercetin as multitarget inhibitors of the Mtb Antigen85 complex.

Lung cancer is a leading global health concern, ranking as the second-highest cause of cancer-related deaths. Tyrosine kinase inhibitors (TKIs) such sorafenib or regorafenib are considered the second-line drugs to treat advanced lung cancer. At advanced stages of lung cancer, the efficacy of TKIs gets reduced and does not produce prolonged effects. Thus, there is a need to discover new ways to increase the efficacy of TKIs for better outcomes. In the present study, synergistic approaches are utilized to improve the anticancer activity of TKIs. We investigated the synergisitic potential of dammarolic acid (DA) with sorafenib in lung cancer cell lines. DA, a triterpenoid derived from Centella asiatica, has demonstrated various medicinal properties. This study explores the combined effects of DA and sorafenib on lung cancer cells focusing on their synergistic mechanisms. To assess this synergy, the half-maximal inhibitory concentration (IC50) of both agents was measured using the MTT assay on lung cancer cell lines. The Chou-Talalay method was applied to calculate synergy parameters and identify effective minimum concentrations. Following this, minimally effective doses of DA and sorafenib were tested to further evaluate cytotoxicity and synergistic potential. Flow cytometric analyses were conducted to measure reactive oxygen species (ROS), mitochondrial membrane potential (MMP), annexin V binding, and cell cycle distribution. Western blotting evaluated autophagy markers LC3-II and p62. Findings indicate that increasing DA concentrations significantly reduced the IC50 and Dose Reduction Index (DRI) values of sorafenib. The co-treatment elevated ROS, disrupted MMP, and increased lung cancer cell cytotoxicity. Overexpression of p62 and LC3-II suggested autophagic inhibition and late apoptosis, confirmed through ATG5 knockdown experiments. Notably, this combination effectively targeted metastatic lung cancer cells by arresting them in the G0/G1 phase, promoting late-stage apoptosis and inhibiting autophagy in metastatic-prone NSCLC cells. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Physiologic changes due to aging, pregnancy, nutritional status, drug interactions, and can affect pharmacokinetics and pharmacodynamics of antiepileptic drugs. In this review article, the interactions between phenytoin and herbs recorded in the literature were summarized according to the Medline database (via PubMed). Our results revealed that, changes in phenytoin's bioavailability were reported for co-administration of herbs or herbal extracts. An increase in phenytoin blood levels was established with Piper nigrum, Mentat, and Lipidum sativum in in vitro and/or in vivo studies. In contrast, herbphenytoin interactions led to sub-therapeutic levels of phenytoin in other cases with herbs such as Cannabis, Ginkgo biloba, Morinda citrifolia, Nigella sativa, and Trigonella foenum graceum. In addition, the findings of other pharmcodynamic experiments showed that various herbs, including Zizyphus jujube, Terminalia chebula, Curcuma longa L, and Centella asiatica, improved the pharmacological impact of phenytoin. To reduce the patients' health risks, health professionals involved in their treatment are expected to be thoroughly educated about the interactions between phenytoin and medicinal plants.

ETHNOPHARMACOLOGICAL RELEVANCE: ECa 233 is a standardized extract of Centella asiatica (L.) Urban, a herb traditionally used to treat a number of diseases including neurological disorders. Accordingly, ECa 233 showed benefits on animal models of cognitive deficits, chronic stress and Parkinson's disease. Analgesic activity of ECa 233 was shown in Tail's flick test in rodent and relieving aphthous ulcer pain in man. Moreover, acute and sub-chronic toxicity testing in rodents and pharmacokinetic study in healthy volunteers, clinical trial phase I demonstrated good safety profiles of ECa 233. AIM OF THE STUDY: This study aims to evaluate the anti-nociceptive effects of ECa 233 and its synergistic effect with gabapentin on chronic neuropathic orofacial pain after 3 weeks infraorbital nerve chronic constriction injury in mice. The peripheral and central nociceptive activities are also examined. MATERIALS AND METHODS: Chronic neuropathic orofacial pain was induced by 3 weeks infraorbital nerve chronic constriction injury. Mice were treated with ECa 233 (30, 100 and 300 mg/kg) and gabapentin (10 mg/kg) by oral gavage starting on day 21 and going on for 14 consecutive days. Mechanical hyperalgesia and allodynia were measured on day 7, 14, 21, 28 and 35 after infraorbital nerve chronic constriction injury. At the end of the experiment, mice were observed for the sedative effect using the locomotor activity, the calcitonin gen-related peptide in trigeminal ganglion and c-fos expression in trigeminal nucleus caudalis were investigated after euthanasia. RESULTS: Infraorbital nerve chronic constriction injury gradually induced marked ipsilateral mechanical hyperalgesia and allodynia. The maximum hyperalgesia and allodynia response presented on day 21 and the response was remained constant until day 35. Treatment with either 300 mg/kg ECa 233 or 10 mg/kg gabapentin were able to attenuate mechanical hyperalgesia and allodynia. The downregulation of calcitonin gen-related peptide on ipsilateral trigeminal ganglion were observed in ECa 233 at 100 and 300 mg/kg and 10 mg/kg gabapentin-treated groups. The c-fos expression on ipsilateral trigeminal nucleus caudalis was also decreas

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (CA) is commonly used herbal medicine for treatment of epilepsy. CA has CYP2C9, CYP2D6 and CYP3A4 enzymes inhibition property and used as an adjuvant therapy with conventional antiepileptic drugs (AEDs). That may be responsible for herb-drug interaction. AIM OF THE STUDY: The present study was planned to evaluate interactions profile of hydroalcoholic extract Centella asiatica (HECA) with antiepileptic drugs in experimental models of epilepsy in rats. MATERIALS AND METHODS: Wistar rats (175-200 g) were used. In the pharmacodynamic interaction study, seizures were induced using pentylenetetrazole (PTZ) (60 mg/kg, i.p.) and maximal electroshock seizure (MES) (70 mA for 0.2 s). The therapeutic and sub-therapeutic doses of valproate (VPA) and phenytoin (PHT) were co-administrated with HECA in PTZ and MES model of seizures respectively. Behavioural parameters were assessed using elevated plus maze test and passive avoidance paradigm. Rat brain oxidative stress parameters were also assessed. In the pharmacokinetic interaction study, the serum levels of the VPA and PHT were estimated at different time intervals by HPLC and pharmacokinetic parameters were analyzed by WinNonlin software. RESULTS: The VPA and PHT produced complete protection against seizures in their therapeutic doses but not with sub-therapeutic doses. However, co-administration of HECA with a sub-therapeutic dose of VPA and PHT enhanced the protection of seizures and significantly (p < 0.001) attenuated the seizure induced oxidative stress and cognitive impairment. It also significantly increased (p < 0.001) serum levels of VPA and PHT. The alterations in pharmacokinetic parameters (maximum serum concentration, area under the curve, clearance) of AEDs were also found with co-administration of HECA. CONCLUSION: The results suggested that co-administration of HECA could improve the therapeutic efficacy of VPA and PHT. But, alteration in pharmacokinetic parameters revel that needs critical medical supervision to avoid any toxic reactions.

Comment in doi: 10.1124/dmd.120.000182. doi: 10.1124/dmd.120.000071. Centella asiatica (CA) shows considerable promise for development as a botanical drug for cognitive decline. Its primary bioactive components include triterpene glycosides asiaticoside and madecassoside and their corresponding aglycones asiatic acid and madecassic acid. Exploration of the bioactivity of CA's caffeoylquinic acids is ongoing. In this study, an aqueous extract of CA (CAW-R61J) was evaluated for drug interaction potential through inhibition or induction of P450 enzymes, as required by the US Food and Drug Administration. CAW-R61J was assessed for induction potential of CYP1A2, CYP2B6, and CYP3A4 using transporter-certified cryopreserved human hepatocytes in sandwich culture. Gene expression of these target P450s was quantified, and enzyme activities were determined to confirm gene expression results. No induction was observed up to 16.7 µg/ml CAW-R61J (equivalent to 1.1 µM asiaticoside, 0.8 µM madecassoside, 0.09 µM asiatic acid, and 0.12 µM madecassic acid). Reversible and time-dependent inhibitory effects of CAW-R61J on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 were evaluated using human liver microsomes. CAW-R61J showed weak reversible inhibition of most of the P450 forms tested, with the strongest being CYP2C9 (IC50 of 330 µg/ml). CAW-R61J (≤1000 µg/ml) was not a time-dependent inhibitor of any of these P450 enzymes. In summary, CAW-R61J had no, or only a weak impact, on P450 induction and inhibition in vitro. The clinical relevance of these results will depend on the in vivo concentration of CAW-R61J components achieved in humans. Plasma triterpene concentrations measured in our recent clinical studies suggest minimal risk of P450-mediated drug interactions by these components. SIGNIFICANCE STATEMENT: A preparation of Centella asiatica is currently under clinical development for the prevention or treatment of cognitive decline. The US Food and Drug Administration required an evaluation of its potential for drug interactions mediated through drug-metabolizing enzymes. This in vitro study revealed minimal induction or inhibition of a range of P450 enzymes, i

To identify alternatives of nerve growth factor, which could promote NF68 protein expression and contribute toward neuronal differentiation, five compounds namely: asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained from Centella asiatica, were examined for their neuronal differentiation effects on PC12 cells. C. asiatica has been applied as an effective herbal medicine for the treatment of various diseases, including depression. According to a statistical design of experiments, both single compound and compound combinations were evaluated. A further statistical analysis indicated quantitative interactions between these five single compounds and led to the identification of the optimal drug combinations. Asiatic acid and madecassic appeared to show profound synergistic effects on neurofilaments expression in vitro. The optimized drug combinations were significantly more potent than single drugs and further investigation suggested that the optimal drug combination could be an analogue of nerve growth factor and could represent a potential treatment for neurodegenerative diseases.

141. Nat Prod Commun. 2015 Nov;10(11):1989-91. Synergy Effects of Three Plant Extracts on Protection of Gastric Mucosa. Wang C, Su W, Su X, Ni G, Liu T, Kong Y. The gastric mucosa protection effect of three natural plant extracts, Hericium erinaceus (HE), Centella asiatica (CA) and Amomum villosum (AV), were evaluated using the indomethacin damage model. Compared with a single extract, a combination of HE/CA/AV, especially with the ratios of 80:10:10, 45:45:10 and 45:10:45, showed significant synergistic effects for protection of the gastric mucosa with gastric ulcer inhibition rates of 97.8 ± 0.7%, 86.5 ± 2.8% and 86.1 ± 3.6%, respectively. Microscopic appearances of the gastric mucosa were carried out to help confirm the results.

The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC). TNF-α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)-dextran. Asiaticoside pretreatment significantly suppressed TNF-α-induced increased permeability. Asiaticoside also prevented TNF-α-induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF-α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti-hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D-induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF-α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F-actin organization.

BACKGROUND: Several herbal drugs and allopathic medicines when co-administered can lead to severe herb-drug interactions. Hence, this study was undertaken in order to assess the in vitro inhibition potential of Withania somnifera and Centella asiatica with cytochrome P450 (CYP) 1A2 and 2C9 enzyme using human liver microsomes. METHODS: Inhibitory potential of crude extracts of both the medicinal plants along with their principal phytoconstituents were investigated using selective probe substrate technique. IC50, Ki values and mode of inhibition were determined. RESULTS: The results of the study revealed that W. somnifera showed no significant interaction with both the isoforms of CYP. However, ethanolic extract of C. asiatica significantly inhibited both CYP1A2 (IC50 value - 42.23±3.65 μg/mL/Ki value - 14.93±4.59 μg/mL) and 2C9 enzyme (IC50 value - 48.41±4.64 μg/mL/Ki value - 23.89±3.14 μg/mL) in a competitive manner. The flavonoids, quercetin and kaempferol showed potent (IC50 values less than 10 μM) inhibition of CYP1A2 activity with no significant inhibition of CYP2C9 enzyme. CONCLUSIONS: Thus, these findings of the study might be helpful for safe and effective use of C. asiatica in clinical practice. However, its in vivo interaction study in humans is still warranted.

Centella asiatica has many applications in cosmetics, including wrinkle treatments, but its effectiveness remains to be clarified. This systematic review study aimed to demonstrate the efficacy and safety of C. asiatica for reducing facial wrinkles. PubMed, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of clinical trials, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Thai Library Integrated System, and Thai university database/journals were searched until May 2019. Five double-blinded randomised controlled trials, including 172 Asian females, were included. Endpoints were wrinkling measured by visual score, image analysis, and participant satisfaction. Two placebo-controlled studies applied gel/creams containing C. asiatica or asiaticoside for 12 w to periorbital skin. Two studies applied tretinoin or Pueraria mirifica contralaterally and by network meta-analysis C. asiatica appeared more effective than P. mirifica but possibly less than tretinoin. Asiaticoside applied as a lipstick for 8 w reduced lip wrinkling. Skin hydration was markedly raised by C. asiatica but not tretinoin. One study reported 10 adverse events for C. asiatica and 35 for tretinoin. Cochrane risk of bias was generally low, reporting was weak, and lack of C. asiatica standardization prevents general application. From the reported data, it is possible to conclude that C. asiatica improved lip and periocular wrinkles, and may replace retinoids if its long-term safety is established and C. asiatica is standardized.

The incidence of cognitive disorders is rising, and medications to address cognitive impairments are limited. Phytochemical compounds have had some success in improving cognitive outcomes in preclinical studies. However, the evidence surrounding the implementation of these compounds routinely in (1) improving cognition in healthy individuals or (2) as prophylaxis and treatment against the cognitive sequelae of neurological insult has not been collated. To address this, the evidence base surrounding the impact of phytochemical agents on cognitive function in healthy individuals was reviewed. Web of Science, PubMed, PsycNET, and AYUSH Research Portal were systematically searched for double-blind and single-blind randomized controlled trials assessing the efficacy of Curcuma longa, Bacopa monnieri, Ocimum tenuiflorum, Camellia sinensis, Centella asiatica, Ganoderma lingzhi, and Rosmarinus officinalis on cognitive function. Seven studies met inclusion. These examined the impact of B. monnieri, O. tenuiflorum, or C. sinensis. There was no benefit of B. monnieri or C. sinensis on processing speed, attention, working memory, language, psychomotor function, or overall cognitive performance. O. tenuiflorum improved reaction times on an executive function task. Further, more methodologically robust trials of longer duration are recommended to investigate the efficacy of phytochemical supplementation for cognition. © The Author(s) 2026. Published by Oxford University Press on behalf of the CINP.

IntroductionThere is no consensus regarding the benefits of venoactive or venotonics drugs such as Micronized Purified Flavonoid Fraction (MPFF) after endovenous therapy. This study aims to address this gap by systematically reviewing the effects of venotonic drugs after endovenous treatments.MethodsA systematic review was conducted, encompassing all relevant studies published up to September 1st 2024. The inclusion criteria were as follows: (1) Initiation of a venotonic drug within 4 weeks or on the same day as undergoing endovenous therapy for lower limb veins; (2) The dosage of venotonic was specified; (3) Any classification of Clinical-Etiology-Anatomy-Pathophysiology (CEAP) was included. Exclusion criteria involved studies that focused solely on the effects of venotonics without the use of endovenous therapy techniques.ResultsSeven studies (four randomized controlled trials, and three cohort studies) involving 1703 (85.9% female) participants were included. The weighted mean age was 41.7 years. Six studies used MPFF, while one study used a combination of diosmin + Centella asiatica+vitamin C. Participants spanned CEAP classifications C1 to C61, with the majority 1210 (71.1%), classified as C1. MPFF showed significant benefits in nine (75.0%) out of 12 assessments when assessed using visual analog scale for pain.ConclusionThe combination of MPFF or diosmin + Centella asiatica + vitamin C with endovenous therapy has been shown to improve pain scores and quality of life compared to groups not receiving venotonics. No studies reported any detrimental effects. However, to establish definitive recommendations regarding the use of venotonics, further randomized, placebo-controlled trials are needed.

BACKGROUND: Cuts and wounds are unfortunate yet inevitable events. Traditional remedies have historically harnessed various plants for wound healing, undergoing clinical and pre-clinical scrutiny. Hence, this systematic review focuses on clinically researched herbal formulations for wound healing. METHODOLOGY: Following Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines, databases like Google Scholar, Web of Science, PubMed, Scopus, J-gate, and Ayush Research Portal were meticulously searched for clinical trials involving wound-targeting herbal formulations, alongside a comprehensive hunt for preclinical plant data. RESULTS: Among 623 screened documents, 26 published clinical trials spotlighting herbal wound healing formulations were identified. All studies showcased significant wound healing progress, with some surpassing standard betadine treatment. Only one study reported an adverse effect. Within the 26 formulations, 45 distinct plant species were employed, with 35 exhibiting wound healing attributes like antimicrobial, anti-inflammatory, and antioxidant activities scientifically. Enhanced collagen content, stabilized fibers, activated fibroblast cells, increased total protein, elevated growth factors, hydroxyproline, hexosamine, and tissue protein demonstrate the efficacy of plants, such as Hypericum perforatum, Centella asiatica, and Calendula officinalis in wound healing. CONCLUSION: The findings of the current study indicated that medicinal plants are effective and safe agents for the treatment of wounds, though larger, well-designed trials are needed for definitive role confirmation.

BACKGROUND: Photoaging is a process of the architecture of normal skin damaged by ultraviolet radiation. Topical cosmeceuticals have been used to treat this condition. The authors aimed to understand the mechanism and level of evidence of different commonly used cosmeceuticals used to treat photodamaged skin. OBJECTIVE: A range of commonly used topical cosmeceuticals (botanicals, peptides, and hydroquinone) has been used in cosmetic medicine for many years to treat photodamaged skin. This review article compares their efficacy and level of evidence. MATERIAL AND METHODS: This study was a systematic review to evaluate the efficacy of different topical cosmeceuticals. Keywords including "Photoaging," "Azelaic acid," "Soy," "Green Tea," "Chamomile," "Ginkgo," "Tea Tree Oil," "Resveratrol," "Cucumber," "Ginseng," "Centella asiatica," "Licorice Root," "Aloe Vera," "Peptides," "Argireline," "Hydroquinone," were typed on OVID, PUBMED, MEDLINE for relevant studies published on photoaging treatment. RESULTS: Most of the evidence behind cosmeceuticals is of high-quality ranging from Level I to Level II. In particular, the evidence base behind peptides is the strongest with most studies achieving Level Ib status in the evidence hierarchy. CONCLUSION: Topical cosmeceuticals like botanicals, peptides and hydroquinone can effectively treat photodamaged skin. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.

BACKGROUND: The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. OBJECTIVE: This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. METHODS: The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. RESULTS: Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1β, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. CONCLUSION: Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

BACKGROUND: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analy

Hepatotoxicity related to HDS is a growing global health issue. We have undertaken a systematic review of published case reports and case series from LA from 1976 to 2020 to describe the clinical features of HDS related hepatotoxicity in this region. We search in PubMed, Web of Science, Scopus and specific LA databases according to PRISMA guidelines. Only HILI cases published in LA that met criteria for DILI definition were included. Duplicate records or reports that lacked relevant data that precluded establishing causality were excluded. Finally, 17 records (23 cases) were included in this review. Centella asiatica, Carthamus tinctorius, and Herbalife® were the most reported HDS culprit products, the main reason for HDS consumption was weight loss. The clinical characteristics of HDS hepatotoxicity in our study were compared to those of other studies in the USA, Europe and China showing a similar signature with predominance of young females, hepatocellular damage, a high rate of ALF and mortality, more frequent inadvertent re-challenge and chronic damage. This study underscores the challenge in causality assessment when multi-ingredients HDS are taken and the need for consistent publication practice when reporting hepatotoxicity cases due to HDS, to foster HDS liver safety particularly in LA. © 2020 John Wiley & Sons, Ltd.