θ-Nanopipette for Single-Cell Resistive-Pulse Profiling of DNA Repair Proteins Accompanied by Drug Evaluation.

Single-cell analysis of the DNA repair protein is important but remains unachieved. Exploration of nanopipettte technologies in single-cell electroanalysis has recently seen rapid growth, while the θ-nanopipette represents an emerging technological frontier with its potential largely veiled. Here a θ-nanopipette is first applied for single-cell resistive-pulse sensing (RPS) of the important DNA repair protein O6-alkylguanine DNA alkyltransferase (hAGT). The removal of alkyl mutations by hAGT could restore the damaged aptamer linking with a structural DNA carrier, allowing the selective binding of the aptamer to thrombin with precisely matched size to produce distinct RPS signals when passing through the orifice. Kinetic analysis of hAGT repair was studied. Meanwhile, the device shows the simultaneous on-demand infusion of inhibitors to inactivate the hAGT activity, indicative of its potential in drug screening for enhanced chemotherapy. This work provides a new paradigm for θ-nanopipette-based single-cell RPS of a DNA repair protein accompanied by drug evaluation.

Microvascularized tumor assembloids model for drug delivery evaluation in colorectal cancer-derived peritoneal metastasis.

Peritoneal metastasis (PM) is a fatal state of colorectal cancer, and only a few patients may benefit from systemic chemotherapy. Although hyperthermic intraperitoneal chemotherapy (HIPEC) brings hope for affected patients, the drug development and preclinical evaluation of HIPEC are seriously lagging behind, mainly due to the lack of an ideal in vitro PM model that makes drug development over-reliant on expensive and inefficient animal experiments. This study developed an in vitro colorectal cancer PM model [microvascularized tumor assembloids (vTA)] based on an assembly strategy of endothelialized microvessels and tumor spheroids. Our data showed that the in vitro perfusion cultured vTA could maintain a similar gene expression pattern to their parental xenografts. Also, the drug penetration pattern of the in vitro HIPEC in vTA could mimic the drug delivery behavior in tumor nodules during in vivo HIPEC. More importantly, we further confirmed the feasibility of constructing a tumor burden-controlled PM animal model using vTA. In conclusion, we propose a simple and effective strategy to construct physiologically simulated PM models in vitro, thus providing a basis for PM-related drug development and preclinical evaluation of locoregional therapies. STATEMENT OF SIGNIFICANCE: This study developed an in vitro colorectal cancer peritoneal metastasis (PM) model based on microvascularized tumor assembloids (vTA) for drug evaluation. With perfusion culture, vTA could maintain a similar gene expression pattern and tumor heterogeneity to their parental xenografts. And the drug penetration pattern in vTA was similar to the drug delivery behavior in tumor nodules under in vivo treatment. Moreover, vTA was more conducive to construct PM animal models with controllable tumor burden. In conclusion, the construction of vTA could provide a new strategy for the PM-related drug development and preclinical evaluation of locoregional therapies.

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Nano-composite system of traditional Chinese medicine for ocular applications: molecular docking and three-dimensional modeling insight for intelligent drug evaluation.

The absorption of drugs was impeded in the posterior part of the eye due to the special structure. In addition, it was crucial to comprehend transport laws of molecules in ocular drug delivery for designing effective strategies. However, the current quality evaluation methods of the eye were backward and lack of dynamic monitoring of drug processes in vivo. Herein, nano-drug delivery system and three-dimensional (3D) model were combined to overcome the problems of low bioavailability and diffusion law. The model drugs were screened by molecular docking. The flexible nano-liposome (FNL) and temperature-sensitive gel (TSG) composite formulation was characterized through comprehensive evaluation. COMSOL software was utilized to build 3D eyeball to predict the bioavailability of drugs. The size of the preparation was about 98.34 nm which is relatively optimal for the enhanced permeability of the eyes. The formulation showed a stronger safety and non-irritant. The pharmacokinetics results of aqueous humor showed that the AUC of two drugs in this system increased by 3.79 and 3.94 times, respectively. The results of 3D calculation model proved that the concentrations of drugs reaching the retina were 1.90×10-5 mol/m3 and 6.37×10-6 mol/m3. In conclusion, the FNL-TSG markedly improved the bioavailability of multiple components in the eye. More importantly, a simplified 3D model was developed to preliminarily forecast the bioavailability of the retina after drug infusion, providing technical support for the accurate evaluation of ocular drug delivery. It provided new pattern for the development of intelligent versatile ophthalmic preparations.

Study on the mechanism of Yupingfeng powder in the treatment of immunosuppression based on UPLC⁃QTOF⁃MS, network pharmacology and molecular biology verification.

AIMS: The current study aims to investigate the effect of Yupingfeng (YPF) powder on immunosuppression, and explore the possible mechanisms. MAIN METHODS: Firstly, the monomer components of YPF powder were analyzed by UPLC-QTOF-MS combined with UNIFI automatic analysis platform, then the mechanism of YPF on immunosuppressive treatment was investigated using network pharmacological method, and finally the prediction was verified in a Candida albicans (Can)-induced immunosuppressive BALB/c mouse model. KEY FINDINGS: 98 monomer compounds in YPF were obtained. Through virtual analysis and screening on the oral utilization and drug likeness properties of the components, 47 effective components were got. 9 core targets obtained were enriched in IL-17 signaling pathway. In the mouse model, YPF could reduce the number of Can and alleviate Can-induced inflammation in the kidney effectively, upregulate Can-induced low proportion of CD4+/CD8+ of splenic lymphocytes, and increase Can-induced low activity of IL-17 pathway. SIGNIFICANCE: These results demonstrate that YPF could improve the immunity of Can-induced immunosuppression in BALB/c mice through upregulating the activity of IL-17 pathway.

Confocal Raman Spectroscopic Imaging for Evaluation of Distribution of Nano-Formulated Hydrophobic Active Cosmetic Ingredients in Hydrophilic Films.

Film-forming systems are highly relevant to the topical administration of active ingredients (AI) to the body. Enhanced contact with the skin can increase the efficacy of delivery and penetration during prolonged exposure. However, after the evaporation of volatile solvents to form a thin film, the distribution of the ingredient should remain homogenous in order to ensure the effectiveness of the formula. This is especially critical for the use of hydrophobic molecules that have poor solubility in hydrophilic films. In order to address this concern, hydroxyphenethyl esters (PHE) of Punica granatum seed oil were prepared as a nanosuspension stabilised by poloxamers (NanoPHE). NanoPHE was then added to a formulation containing polyvinyl alcohol (PVA) as a film forming agent, Glycerol as a plasticiser and an antimicrobial agent, SepicideTM HB. Despite their reliability, reference methods such as high-performance liquid chromatography are increasingly challenged due to the need for consumables and solvents, which is contrary to current concerns about green industry in the cosmetics field. Moreover, such methods fail to provide spatially resolved chemical information. In order to investigate the distribution of ingredients in the dried film, Confocal Raman imaging (CRI) coupled to Non-negatively Constrained Least Squares (NCLS) analysis was used. The reconstructed heat maps from a range of films containing systematically varying PHE concentrations highlighted the changes in spectral contribution from each of the ingredients. First, using NCLS scores it was demonstrated that the distributions of PVA, Glycerol, SepicideTM HB and PHE were homogenous, with respective relative standard deviations (RSD) of 3.33%, 2.48%, 2.72% and 6.27%. Second, the respective relationships between ingredient concentrations in the films and their Raman responses, and the spectral abundance were established. Finally, a model for absolute quantification for PHE was be constructed using the percentage of spectral abundance. The prepared %w/w concentrations regressed against predicted %w/w concentrations, displaying high correlation (R2 = 0.995), while the Root Mean Squared Error (0.0869% w/w PHE) confirmed the precision of the analysis. The mean percent relative error of 3.75% indicates the accuracy to which the concentration in dried films could be determined, further supporting the suitability of CRI for analysis of composite solid film matrix. Ultimately, it was demonstrated that nanoformulation of hydrophobic PHE provides homogenous distribution in PVA based film-forming systems independent of the concentration of NanoPHE used in the formula.

Optimization of Pressurized Liquid Extraction and In Vitro Neuroprotective Evaluation of Ammodaucus leucotrichus. Untargeted Metabolomics Analysis by UHPLC-MS/MS.

Ammodaucus leucotrichus is a spontaneous plant endemic of the North African region. An efficient selective pressurized liquid extraction (PLE) method was optimized to concentrate neuroprotective extracts from A. leucotrichus fruits. Green solvents were tested, namely ethanol and water, within a range of temperatures between 40 to 180 °C. Total carbohydrates and total phenolics were measured in extracts, as well as in vitro antioxidant capacity (DPPH radical scavenging), anticholinesterase (AChE) and anti-inflammatory (LOX) activities. Metabolite profiling was carried out by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-q-TOF-MS/MS), identifying 94 compounds. Multivariate analysis was performed to correlate composition with bioactivity. A remarkable effect of the temperature using water was observed: the higher temperature, the higher extraction yield, the higher total phenolic content, as well as the higher total carbohydrates content. The water extract obtained at 180 °C, 10.34 MPa and 10 min showed meaningful anti-inflammatory (IC50LOX = 39.4 µg/mL) and neuroprotective activities (IC50AChE = 55.6 µg/mL). The Principal Components Analysis (PCA) and the cluster analysis correlated these activities with the presence of carbohydrates and phenolic compounds.

Nicotinamide riboside has minimal impact on energy metabolism in mouse models of mild obesity.

Supplementation with precursors of NAD has been shown to prevent and reverse insulin resistance, mitochondrial dysfunction, and liver damage in mouse models of diet-induced obesity. We asked whether the beneficial effects of supplementation with the NAD precursor nicotinamide riboside (NR) are dependent on mouse strain. We compared the effects of NR supplementation on whole-body energy metabolism and mitochondrial function in mildly obese C57BL/6N and C57BL/6J mice, two commonly used strains to investigate metabolism. Male C57BL/6N and C57BL/6J mice were fed a high-fat diet (HFD) or standard chow with or without NR supplementation for 8 weeks. Body and organ weights, glucose tolerance, and metabolic parameters as well as mitochondrial O2 flux in liver and muscle fibers were assessed. We found that NR supplementation had no influence on body or organ weight, glucose metabolism or hepatic lipid accumulation, energy expenditure, or metabolic flexibility but increased mitochondrial respiration in soleus muscle in both mouse strains. Strain-dependent differences were detected for body and fat depot weight, fasting blood glucose, hepatic lipid accumulation, and energy expenditure. We conclude that, in mild obesity, NR supplementation does not alter metabolic phenotype in two commonly used laboratory mouse strains.

[Current status of drug safety evaluation using zebrafish].

In recent years, the success rate of drug development has declined, and along with it, R&D costs have continued to rise. The rate of discontinuation of drug development due to safety reasons remains unchanged from 20 years ago. Therefore, it is important to check the safety of candidate compounds early in drug discovery in order to improve drug discovery efficiency. Under such circumstances, each company is focusing on establishing a low-cost, high-precision, and high-throughput safety screening system. The zebrafish is expected as a new experimental animal that serves as a bridge between in vitro and in vivo, and the progress of research in the last 15 years has been remarkable. At present, zebrafish are becoming a major experimental animal in Japan. At the same time, the gap between ideal and reality began to be seen, and it was time to once again understand the characteristics of zebrafish and think about its usage. This paper summarizes the points to be noted in the screening using zebrafish and introduces the use for actual safety evaluation.

Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail.

The botanical natural product goldenseal can precipitate clinical drug interactions by inhibiting cytochrome P450 (CYP) 3A and CYP2D6. Besides P-glycoprotein, effects of goldenseal on other clinically relevant transporters remain unknown. Established transporter-expressing cell systems were used to determine the inhibitory effects of a goldenseal extract, standardized to the major alkaloid berberine, on transporter activity. Using recommended basic models, the extract was predicted to inhibit the efflux transporter BCRP and uptake transporters OATP1B1/3. Using a cocktail approach, effects of the goldenseal product on BCRP, OATP1B1/3, OATs, OCTs, MATEs, and CYP3A were next evaluated in 16 healthy volunteers. As expected, goldenseal increased the area under the plasma concentration-time curve (AUC0-inf ) of midazolam (CYP3A; positive control), with a geometric mean ratio (GMR) (90% confidence interval (CI)) of 1.43 (1.35-1.53). However, goldenseal had no effects on the pharmacokinetics of rosuvastatin (BCRP and OATP1B1/3) and furosemide (OAT1/3); decreased metformin (OCT1/2, MATE1/2-K) AUC0-inf (GMR, 0.77 (0.71-0.83)); and had no effect on metformin half-life and renal clearance. Results indicated that goldenseal altered intestinal permeability, transport, and/or other processes involved in metformin absorption, which may have unfavorable effects on glucose control. Inconsistencies between model predictions and pharmacokinetic outcomes prompt further refinement of current basic models to include differential transporter expression in relevant organs and intestinal degradation/metabolism of the precipitant(s). Such refinement should improve in vitro-in vivo prediction accuracy, contributing to a standard approach for studying transporter-mediated natural product-drug interactions.

Network Pharmacology Study of the Hepatoprotective Effects of Quercetin-Containing Traditional Chinese Medicine, Anoectochilus roxburghii, and Validation of Quercetin as an Anti-Liver Injury Agent in a Mouse Model of Liver Injury.

BACKGROUND Anoectochilus roxburghii (Orchidaceae) (AR) has been widely used to treat liver injury in China, but its underlying mechanisms remain elusive. Network pharmacology was utilized to assess the hepatoprotective effects of quercetin (Que)-containing AR, and to validate the anti-liver injury effects of Que in a mouse model of liver injury. MATERIAL AND METHODS Network pharmacology analysis was performed to determine bio-active compounds in AR. The core therapeutic targets of AR against liver injury were identified using a protein-protein interaction network. Biological function and pathway enrichment were analyzed based on the identified core therapeutic targets. The hepatoprotective effects of Que in a mouse model of liver injury induced by CCl4 were assessed to verify the reliability of network pharmacology analysis. RESULTS Seven bio-active compounds of AR met drug screening criteria and 17 core therapeutic targets of AR against liver injury were identified. Biological function analysis demonstrated that the therapeutic effects of AR against liver injury were chiefly associated with the suppression of inflammation and immunity; and pathway enrichment analysis showed that nuclear factor-kappa B (NF-kappaB) and tumor necrosis factor (TNF) signaling pathways were associated with the inflammatory responses. Experimental validation in a mouse model showed that AR exerted anti-inflammatory effects by regulating the NF-kappaB signaling pathway, a finding that also confirmed the reliability of network pharmacology analysis. CONCLUSIONS The bio-active compounds identified in AR and the elucidation of their mechanisms of action against liver injury provide a theoretical basis for designing agents that can prevent or suppress liver injury.

Effect of lubiprostone on vinca alkaloid-induced constipation in patients with hematological malignancies: a propensity score-matched analysis.

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

Combined chelation with high-dose deferiprone and deferoxamine to improve survival and restore cardiac function effectively in patients with transfusion-dependent thalassemia presenting severe cardiac complications.

Iron overload-induced cardiomyopathy is the leading cause of death in patients with transfusion-dependent thalassemia (TDT). The mortality is extremely high in these patients with severe cardiac complications, and how to rescue them remains a challenge. It is reasonable to use combined chelation with deferiprone (L1) and deferoxamine (DFO) because of their shuttle and synergistic effects on iron chelation. Here, seven consecutive patients with TDT who had severe cardiac complications between 2002 and 2019 and received combined chelation therapy with oral high-dose L1 (100 mg/kg/day) and continuous 24-h DFO infusion (50 mg/kg/day) in our hospital were reported. Survival for eight consecutive patients receiving DFO monotherapy for their severe cardiac complications between 1984 and 2001 was compared. We found that combined chelation therapy with high-dose L1 and DFO was efficient to improve survival and cardiac function in patients with TDT presenting severe cardiac complications. Reversal of arrhythmia to sinus rhythm was noted in all patients. Their 1-month follow-up left ventricular ejection fraction increased significantly (P < 0.001). There were no deaths, and all patients were discharged from hospital with good quality of life. In contrast, all the eight patients receiving DFO monotherapy died (P < 0.001). Accordingly, combined chelation therapy with high-dose L1 and DFO should be considered in patients with TDT presenting cardiac complications.

Bioengineering tools to speed up the discovery and preclinical testing of vaccines for SARS-CoV-2 and therapeutic agents for COVID-19.

This review provides an update for the international research community on the cell modeling tools that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could thus speed up the development of vaccines and therapeutic agents against COVID-19. Many bioengineering groups are actively developing frontier tools that are capable of providing realistic three-dimensional (3D) models for biological research, including cell culture scaffolds, microfluidic chambers for the culture of tissue equivalents and organoids, and implantable windows for intravital imaging. Here, we review the most innovative study models based on these bioengineering tools in the context of virology and vaccinology. To make it easier for scientists working on SARS-CoV-2 to identify and apply specific tools, we discuss how they could accelerate the discovery and preclinical development of antiviral drugs and vaccines, compared to conventional models.

The traditional use of southern African medicinal plants in the treatment of viral respiratory diseases: A review of the ethnobotany and scientific evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral respiratory infections are amongst the most common infections globally, with most of the world's population contracting at least one infection annually. Numerous plant species are used in traditional southern African healing systems to treat these diseases and to alleviate the symptoms. Despite this, the therapeutic potential of these plants against viral respiratory diseases remains poorly explored. AIM OF THE STUDY: The aim of this study was to document the southern African plant species used in traditional medicine to treat viral respiratory infections. We also examined the extent of scientific evaluations of southern African plant species against the respiratory-infective viruses, with the aim of stimulating interest in this area and focusing on future studies. MATERIALS AND METHODS: We undertook an extensive review of ethnobotanical books, reviews and primary scientific studies to identify southern African plants which are used in traditional southern African medicine to treat viral respiratory diseases. This information was used to identify gaps in the current research that require further study. RESULTS: Two hundred and fifty-seven southern African plant species were identified as traditional therapies for viral respiratory diseases. Surprisingly, only one of those species (as well as twenty-one other species not recorded for these purposes) has been evaluated for the ability to block respiratory virus production. Furthermore, most of these studies screened against a single viral strain and none of those studies examined the mechanism of action of the plant preparations. CONCLUSIONS: Despite well documented records of the use of southern African plants to treat respiratory viral diseases, the field is poorly explored. Nearly all of the plant species used in traditional healing systems to treat these diseases are yet to be tested. Substantial further work is required to verify the efficacy of these traditional medicines.

The traditional use of southern African medicinal plants for the treatment of bacterial respiratory diseases: A review of the ethnobotany and scientific evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Multiple plant species were used traditionally in southern Africa to treat bacterial respiratory diseases. This review summarises this usage and highlights plant species that are yet to be verified for these activities. AIM OF THE STUDY: This manuscript reviews the traditional usage of southern African plant species to treat bacterial respiratory diseases with the aim of highlighting gaps in the literature and focusing future studies. MATERIALS AND METHODS: An extensive review of ethnobotanical books, reviews and primary scientific studies was undertaken to identify southern African plants which are used in traditional southern African medicine to treat bacterial respiratory diseases. We also searched for southern African plants whose inhibitory activity against bacterial respiratory pathogens has been conmfirmed, to highlight gaps in the literature and focus future studies. RESULTS: One hundred and eighty-seven southern African plant species are recorded as traditional therapies for bacterial respiratory infections. Scientific evaluations of 178 plant species were recorded, although only 42 of these were selected for screening on the basis of their ethnobotanical uses. Therefore, the potential of 146 species used teraditionally to treat bacterial respiratory diseases are yet to be verified. CONCLUSIONS: The inhibitory properties of southern African medicinal plants against bacterial respiratory pathogens is relatively poorly explored and the antibacterial activity of most plant species remains to be verified.

Pharmaceutical evaluation of Graphirine syrup formulated from some common indigenous herbs of Pakistan.

Since ancient times humans have relied on traditional medicine and herbal formulation for the cure of various diseases and disorders. Globally, interest in use of herbal medicine has increased; as drawbacks of modern medicine and have started getting more prominent. Most of the traditional system of medicine; all in their formulations depends on plants. Traditional herbal cough products have considered to be mild, nontoxic, non-sedative and even harmless. As Syrup is commonly taken for the relief of cough; we aimed to formulate a cough syrup (Graphirine) from some common indigenous herbs; Adhatoda vasica, Piper longum and Rosa Damasena and evaluate its physicochemical parameters along with the changes in accelerated stability testing. Preformulation studies, i.e. moisture content, ash, water and ethanol extractive values of all three herbs were defined. Physicochemical factors, quantitative spectral measurement, FTIR spectrum for identification of compounds; along with accelerated stability and possible microbial fungal growth; were also checked for the formulated syrup. Each and every parameter complied with the specifications.

Evaluation of anti-inflammatory and wound healing potential of tannins isolated from leaf callus cultures of Achyranthes aspera and Ocimum basilicum.

Herbal medicines are important in treatment of inflammation as they are safe and nontoxic. Tannins are important bioactive compounds used as anti-inflammatory agents and possess wound healing potential. Anti-inflammatory activity of tannins extracted from seedling leaf tissue and callus culture extracts of Achyranthes aspera L. and Ocimum basilicum L. were determined using Carrageenan induced paw edema model. Wound healing potential of tannins from callus cultures of leaf explants of both plants were evaluated using four models in rabbits i.e. excision, incision, dead space and burn wound. Group I acted as control, Group II treated with Povidone iodine as standard drug. Groups III and IV were experimental groups treated with creams which consisted of tannins of callus cultures of leaf; cream A (A. aspera) and cream O (O. basilicum). The results of anti-inflammatory activity of callus cultures of leaf explants were comparable with standard drug Indomethacin. Seedling leaf tissue and callus culture extracts of A. aspera and O. basilicum plant showed decrease in paw edema thickness, size and maximum percentage inhibition of paw edema respectively. Among four wound models burn wound showed the best wound contraction by Cream O. Hydroxyproline content and tensile strength of dead space and incision wounds exhibited good result also respectively. Cream O exhibited best results as compared to cream A. Histopathological examination showed that cream O showed faster rate of fibroblast and collagen formation as compared to cream A. The results showed that condensed tannins of callus cultures of leaf of A. aspera exhibited the best anti-inflammatory activity while tannins from callus cultures O. basilicum showed the best results for wound healing. These findings may enable use of both plants for formulation of new phytomedicine.