The Ameliorative Effect of Litsea martabanica (Kurz) Hook. f. Leaf Water Extract on Chlorpyrifos-Induced Toxicity in Rats and Its Antioxidant Potentials.

Litsea martabanica root's antioxidant and acetylcholinesterase (AChE) activity showed promise as a pesticide detoxification agent in our previous study. In addition to its root, leaves can help alleviate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in several countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally used leaves instead of roots. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extract from L. martabanica leaves through in vitro and in vivo investigations. In the in vitro study, L. martabanica water extract and its fractions demonstrated antioxidant activity and induced apoptosis in hepatic satellite cells. In the in vivo study, treatment with the leaf extract led to increased AChE activity, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) levels, and reduced glutathione in chlorpyrifos-exposed rats. Histopathological examination revealed that chlorpyrifos-treated rats exhibited liver cell damage, while treatment with the water extract of L. martabanica exhibited a protective effect on the liver. In conclusion, L. martabanica water extract exhibited antioxidant activity, enhanced AChE activity, and improved histopathological abnormalities in the liver.

Polymer Matrix and Manufacturing Methods in Solid Dispersion System for Enhancing Andrographolide Solubility and Absorption: A Systematic Review.

Background: Andrographolide (ADG) has poor aqueous solubility and low bioavailability. This study systematically reviews the use of solid dispersion (SD) techniques to enhance the solubility and absorption of ADG, with a focus on the methods and polymers utilized. Methodology: We searched electronic databases including PubMed, Web of Science, Scopus®, Embase and ScienceDirect Elsevier® up to November 2023 for studies on the solubility or absorption of ADG in SD formulations. Two reviewers independently reviewed the retrieved articles and extracted data using a standardized form and synthesized the data qualitatively. Results: SD significantly improved ADG solubility with up to a 4.7-fold increase and resulted in a decrease in 50% release time (T1/2) to less than 5 min. SD could also improve ADG absorption, as evidenced by higher Cmax and AUC and reduced Tmax. Notably, Soluplus-based SDs showed marked solubility and absorption enhancements. Among the five SD techniques (rotary evaporation, spray drying, hot-melt extrusion, freeze drying and vacuum drying) examined, spray drying emerged as the most effective, enabling a one-step process without the need for post-milling. Conclusions: SD techniques, particularly using Soluplus and spray drying, effectively enhance the solubility and absorption of ADG. This insight is vital for the future development of ADG-SD matrices.

Essential oil pharmaceuticals for killing ectoparasites on dogs.

BACKGROUND: External parasites, particularly ticks and fleas, are among the most common problems affecting dogs. Chemical medicines are commonly used to prevent and eliminate such external parasites, but their improper use can cause adverse reactions, and the toxins they contain may remain in the environment. OBJECTIVES: The objective of this study was to investigate the in vitro efficacy of Zanthoxylum limonella, citronella, clove, peppermint, and ginger essential oils against dog ticks and fleas and to test the sensitivity of dogs' skin to these essential oils. METHODS: The five essential oils were tested for in vitro efficacy against ticks and fleas, and the two most effective essential oils were then tested on the dogs' skin. RESULTS: The results revealed that these five essential oils at 16% concentrations effectively inhibited the spawning of female engorged ticks. In addition, all five essential oils had a strong ability to kill tick larvae at concentrations of 2% upward. Furthermore, 4% concentrations of the five essential oils quickly eliminated fleas, especially clove oil, which killed 100% of fleas within 1 h. A 50%, 90%, and 99% lethal concentration (LC50, LC90, and LC99) for the essential oils on tick larvae in 24 h were found to be low values. LC50, LC90, and LC99 for the essential oils on flea in 1 h was lowest values. Clove oil at 16% concentration was the most satisfactory essential oil for application on dogs' skin, with a low percentage of adverse effects. CONCLUSIONS: This study confirmed the effectiveness of essential oils for practical use as tick and flea repellents and eliminators. Essential-oil-based pharmaceutical can replace chemical pesticides and provide benefits for both consumers and the environment.

Gastroprotective effects of Pikad Tri-phol-sa-mut-than herbal remedy on multiple gastric ulcer models in rats.

In Thai traditional medicine, Pikad Tri-phol-sa-mut-than has long been used to alleviate gastrointestinal symptoms, renal disease, inflammation-related disorders, and severe malady. This recipe is composed of dried fruits of Morinda citrifolia L., Coriandrum sativum L., and Aegle marmelos (L.) Corrêa. The aim of this study was to assess the anti-gastric ulcer property of the water extract of Pikad Tri-phol-sa-mut-than (TS), using various animal models with different inducers, including restraint water immersion stress, indomethacin, and ethanol/hydrochloric acid (EtOH/HCl). Its mechanisms of anti-gastric ulcer actions were also elucidated using both in vitro and in vivo experiments. When compared with the control groups, the oral pretreatment of TS at the doses of 150, 300 and 600 mg/kg significantly reduced the gastric ulcer formation in all models. It was also found that TS at the dose of 600 mg/kg could increase gastric wall mucus in rats but could not produce the significant reduction of the gastric volume or total acidity of gastric content. Results from hematoxylin and eosin (H&E) and Periodic acid-Schiff (PAS) staining examinations of gastric tissues confirmed that TS visibly reduced gastric mucosal damage, while immunohistochemistry revealed that TS remarkably suppressed the protein expression of Bcl-2-associated X (BAX), a regulator of apoptosis, compared to those of the control group. The DPPH, ABTS, and FRAP assays showed antioxidant effects of TS. All of these findings demonstrated that TS has gastroprotective effects, which may be related to the increase in the gastric wall mucus secretion, not anti-secretory activity, as well as its antioxidant and antiapoptotic activities.

Anti-Inflammatory, Antinociceptive, Antipyretic, and Gastroprotective Effects of Eurycoma longifolia Jack Ethanolic Extract.

Tongkat ali (Eurycoma longifolia Jack) (ELJ) is a plant in the Simaroubaceae family. Its roots are used in traditional Thai medicine to treat inflammation, pain, and fever; however, the antiulcer abilities of its ethanolic extract have not been studied. This study examined the anti-inflammatory, antinociceptive, antipyretic, and gastroprotective effects of ethanolic ELJ extract in animal models and found that ELJ effectively reduced EPP-induced ear edema in a dose-dependent manner and that a high dose of ELJ inhibited carrageenan-induced hind paw edema formation. In cotton-pellet-induced granuloma formation, a high dose of ELJ suppressed the increases in wet granuloma weight but not dry or transudative weight. In the formalin-induced nociception study, ELJ had a significant dose-dependent inhibitory impact. Additionally, the study found that yeast-induced hyperthermia could be significantly reduced by antipyretic action at the highest dose of ELJ. In all the gastric ulcer models induced by chemical substances or physical activity, ELJ extracts at 150, 300, and 600 mg/kg also effectively prevented gastric ulcer formation. In the pyloric ligation model, however, the effects of ELJ extract on gastric volume, gastric pH, and total acidity were statistically insignificant. These findings support the current widespread use of Eurycoma longifolia Jack in traditional medicine, suggest the plant's medicinal potential for development of phytomedicines with anti-inflammatory, antinociceptive, and antipyretic properties, and support its use in the treatment of gastric ulcers due to its gastroprotective properties.

HPLC and DNA barcoding profiles for identification of the selected twelve Mucuna species and its application for detecting prohibited aphrodisiac Mucuna products.

Aphrodisiac herbal products originated from various plants including Mucuna species. In Thai folklore, Mucuna macrocarpa Wall. and M. pruriens (L.) DC. have long been consumed and utilized for their aphrodisiac properties. Consumption of these plants can lead to serious adverse effects caused by l-dopa. The plants have been legally banned for use as foods, dietary supplements, or nutraceuticals by the FDA of several countries. To protect consumers, methods for the identification of illicit plants or herbal products are needed. This study aimed to identify the selected twelve Mucuna species and examine the aphrodisiac herbal products containing M. macrocarpa and M. pruriens by using HPLC analysis of l-dopa coupled with DNA barcoding profiles of ITS, matK, rbcL, and trnH-psbA. The results showed that l-dopa could be found not only in the seeds of M. macrocarpa and M. pruriens but also in associated allied Mucuna species. Then, a DNA barcode was introduced to support in HPLC profiling to identify the plants. DNA barcodes of twelve Mucuna species found in Thailand were established and used to reconstruct a phylogenetic tree. In this study, ITS2 sequences showed the highest interspecific variability and could be used to differentiate all Mucuna species. The results of ITS2 sequence coupled with HPLC analysis revealed that all the purchased aphrodisiac products originated from M. pruriens only. Therefore, the integration of HPLC analysis and DNA barcoding profile was an efficient method for the identification of prohibited Mucuna species for safety monitoring of herbal supplements and protecting customer safety. Regulatory agencies should raise awareness and restrain the use of these commercial products.

Anti-inflammatory effects of Pikad Tri-phol-sa-mut-than remedy, consisting of dried fruits of Aegle marmelos (L.) Corrêa, Coriandrum sativum L., and Morinda citrifolia L.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation has been known to possess some essential roles in many diseases, especially those with chronic or severe conditions. Pikad Tri-phol-sa-mut-than, a Thai traditional herbal remedy, has long been used to treat gastrointestinal sicknesses, fever, and severe illness caused by the deformities of Tridosha. In particular, this recipe has also been applied for inflammation-related conditions including gout and rheumatoid arthritis. The Pikad Tri-phol-sa-mut-than recipe consists of dried fruits of three herbs including Aegle marmelos (L.) Corrêa, Morinda citrifolia L., and Coriandrum sativum L. Each of these plant components of Pikad Tri-phol-sa-mut-than exhibited anti-inflammatory activities. However, anti-inflammatory effect of Pikad Tri-phol-sa-mut-than remedy has not been reported. AIM OF THE STUDY: The objective of this study was to elucidate the anti-inflammatory activities of Pikad Tri-phol-sa-mut-than extract (TS) against acute and chronic inflammation in rats. MATERIALS AND METHODS: To study the effects of TS on acute inflammation, ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema models were carried out. In addition, cotton pellet-induced granuloma formation was performed to specify the inhibitory effects of TS on chronic inflammation. RESULTS: The topical application of TS significantly inhibited EPP-induced ear edema in rats. In the carrageenan- and AA-induced paw edema models, the oral administration of TS significantly reduced paw volumes, compared to those of the control groups. In addition, the 7-day oral treatment of TS demonstrated a significant suppressive effect on cotton pellet-induced granuloma formation. CONCLUSIONS: The current study revealed that TS possesses anti-inflammatory activities against acute and chronic inflammation. Our studies support the use of TS in traditional medicine, and the development of TS as a novel natural product for treating diseases associated with inflammation.

The Leaf Extract of Mitrephora chulabhorniana Suppresses Migration and Invasion and Induces Human Cervical Cancer Cell Apoptosis through Caspase-Dependent Pathway.

Cervical cancer is rated to be the leading cause of cancer-related death in women worldwide. Since screening test and conventional treatments are less accessible for people in developing countries, an alternative use of medicinal plants exhibiting strong anticancer activities may be an affordable means to treat cervical cancer. Mitrephora chulabhorniana (MC) is the newly identified species; however, its biological functions including anticancer activities have been largely unexplored. Hence, in this study, we were interested in investigating anticancer effects of this plant on the human cervical cell line (HeLa). MC extract was profiled for phytochemicals by TLC. This plant was tested to contain alkaloids, flavonoids, and terpenes. HeLa cells were treated with MC extract to investigate the anticancer activities. Cytotoxicity and viability of cells treated with MC were determined by MTT assay and Trypan blue exclusion assay. Cell migration was tested by wound healing assay, and cell invasion was determined by Transwell assay. The level of caspase 7, caspase 9, and PARP was determined by western blot analysis. We found that the leaf extract of MC strongly reduced cancer cell survival rate. This finding was consistent with the discovery that the extract dramatically induced apoptosis of cervical cancer cells through the activation of caspase 7 and caspase 9 which consequently degraded PARP protein. Furthermore, MC extract at lower concentrations which were not cytotoxic to the cancer cells showed potent inhibitory activities against HeLa cervical cancer cell migration and invasion. Mitrephora chulabhorniana possesses its pharmacological properties in inhibiting cervical cancer cell migration/invasion and inducing apoptotic signaling. This accumulated information suggests that Mitrephora chulabhorniana may be a beneficial source of potential agents for cervical cancer treatment.

Antiallergic activities of shallot (Allium ascalonicum L.) and its therapeutic effects in allergic rhinitis.

BACKGROUND: Onion has antiallergic activity but lack of evidence for shallot. OBJECTIVE: To determine whether shallot owns similar antiallergic activity to onion and its therapeutic effects in allergic rhinitis when added to standard treatment. METHODS: In-vitro ß-hexosaminidase inhibitory activities of shallot was compared with onion on RBL-2H3 cells. In clinical study, a randomized, double-blind, placebo-controlled trial was performed. Sixteen AR patients were randomized equally into the controls who received cetirizine 10 mg once daily and placebo capsules for 4 weeks, and the treatment who received 3g of oral shallot per day (equivalent to 1 ½ bulbs) and cetirizine. Visual analog scores of overall symptoms (VAS), total nasal and ocular symptom scores (TNSS and TOSS), nasal airway resistance (NAR), and adverse events were assessed. RESULTS: Shallot extract at 200 µg/mL had an average ß-hexosaminidase inhibition rate of 97% while onion extract had 73%. HPLC chromatograms (λ = 290nm) of both plants showed nearly identical patterns of quercetin compounds, such as quercetin 3,4'-diglucoside, quercetin 4'-glucoside, and quercetin. After 4-week of treatment, 62.5% of patients in shallot group and 37.5% of patients in control group showed improvement of post-treatment VAS. TNSS were significantly reduced in both groups, however no difference between groups (P = 0.18). TOSS were significantly improved only in the shallot group (P = 0.01). Adverse events from shallot were not different from placebo. CONCLUSIONS: Shallot had antiallergic activity and similar quercetin compounds to onion. The shallot oral supplement and cetirizine was shown to improve the overall AR symptoms more than cetirizine alone.

Clinical Pilot Study of Rectal Suppository Containing Combined Extract of Cissus quadrangularis Linn. and Acmella paniculata (Wall ex. DC.) R. K. Jansen in Acute Hemorrhoids.

BACKGROUND: Cissus quadrangularis Linn. (CQ) is a medicinal plant with good evidence for the treatment of hemorrhoids, listed in the Thai National List of Herbal Products in the oral dosage form. Acmella paniculata (Wall ex. DC.) R. K. Jansen. (AP) is a medicinal plant with a local anesthetic effect. OBJECTIVE: To investigate the potential of rectal suppositories containing CQ and AP extracts to alleviate symptoms of hemorrhoids compared with the commercialized rectal suppository containing hydrocortisone and cinchocaine. MATERIALS AND METHODS: Hemorrhoid outpatients (n = 105) with different severity grades (I, II, or III) from eight hospitals in northern Thailand were included in this study. Hemorrhoid severity was graded by proctoscopy associated with either anal pain or bleeding related to hemorrhoids or both. The patients were randomly allocated to two groups: CQ-AP group (n = 52) or the commercialized rectal suppository group (n = 53). One suppository was rectally administered twice daily in the morning and at bedtime for seven days. Evaluations were performed by physicians on days 1, 4, and 8 of the study. The primary endpoints were bleeding and prolapse size, while the secondary endpoint was anal pain. RESULTS: Baseline demographics, lifestyle, constipation, number of prolapses, grade of hemorrhoid severity, and duration of experiencing hemorrhoids were comparable in both groups of patients. The effects of CQ-AP and the commercialized rectal suppository on bleeding, prolapse size, and anal pain were comparable. The patients in both groups were satisfied with both products at comparable levels and stated a preference for further use in the case of hemorrhoids recurrence. In terms of safety, the patients in the commercialized rectal suppository group experienced a higher incidence of adverse events, including anal pain and bleeding. CONCLUSION: Rectal suppositories containing a combined extract of CQ and AP show potential in alleviating hemorrhoidal symptoms with a good safety profile.

Specification and DNA Barcoding of Thai Traditional Remedy for Chronic Kidney Disease: Pikad Tri-phol-sa-mut-than.

The Pikad Tri-phol-sa-mut-than (TS) remedy, a Thai traditional medicine, is officially recorded in Tamra Paetsart Sonkrau Chabub Anurak for its capabilities in treating kidney deficiency. TS remedy is composed of three fruit species-Aegle marmelos (L.) Corrêa., Coriandrum sativum L., and Morinda citrifolia L.-in an equal part by weight. The quality of the raw material is one of the essential factors that can affect the effectiveness and safety of treatment by herbal remedy. The pharmacognostic evaluation and DNA barcode of the three fruit species and TS remedy were performed in this study to authenticate them from contamination, and to provide the scientific database for further uses. Macroscopic and microscopic examination, chemical profile by TLC, and DNA barcoding were employed to positively identify the raw materials bought from the herbal market, especially the powder form. Consequently, the outcomes of this investigation can be used to develop an essential and effective tool for the authentication of crude drugs and herbal remedies.

Topical Gynura procumbens as a Novel Therapeutic Improves Wound Healing in Diabetic Mice.

Nonhealing wounds are major socioeconomic challenges to healthcare systems worldwide. Therefore, there is a substantially unmet need to develop new drugs for wound healing. Gynura procumbens, a herb found in Southeast Asia, may be an effective therapeutic for nonhealing diabetic wounds. The aim of this study was to evaluate the efficacy of G. procumbens on wound healing in the diabetic milieu. G. procumbens extract was obtained using 95% ethanol and its components were determined by thin layer chromatography. Diabetes was induced in mice using streptozotocin. We found that G. procumbens extract contained stigmasterol, kaempferol and quercetin compounds. Topical application of G. procumbens on the wounded skin of diabetic mice accelerated wound healing and induced the expression of angiogenin, epidermal growth factor, fibroblast growth factor, transforming growth factor and vascular endothelial growth factor. Furthermore, G. procumbens promoted in vitro wound healing and enhanced the migration and/or proliferation of human endothelial cells, fibroblasts, keratinocytes and mast cells cultured in diabetic conditions. Finally, G. procumbens promoted vascular formation in the diabetic mice. To the best of our knowledge, this is the first study that evaluates in vivo wound healing activities of G. procumbens and activation of cells involved in wound healing process in diabetic conditions. The findings that G. procumbens accelerates wound healing and activates cells involved in the wound healing process suggest that G. procumbens might be an effective alternative therapeutic option for nonhealing diabetic wounds.

In Vitro Antioxidant Activity of Litsea martabanica Root Extract and Its Hepatoprotective Effect on Chlorpyrifos-Induced Toxicity in Rats.

In Thailand, people in the highland communities whose occupational exposure to pesticides used the root of Litsea martabanica as a detoxifying agent. However, the scientific data to support the traditional use of this plant are insufficient. This study aimed to evaluate the antioxidant activity and anti-pesticide potential of L. martabanica root extract. Antioxidant properties were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radicals scavenging assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), and total phenolic content determination. In all assays, L. martabanica extracts and their fractions exhibited high antioxidant activities differently. The water extract is traditionally used as a detoxifying agent. Therefore, it was chosen for in vivo experiments. The rats received the extract in a way that mimics the traditional methods of tribal communities followed by chlorpyrifos for 16 days. The results showed that acetylcholinesterase activity decreases in pesticide-exposed rats. Treatment with the extract caused increasing acetylcholinesterase activity in the rats. Therefore, L. martabanica extract may potentially be used as a detoxifying agent, especially for the chlorpyrifos pesticide. The antioxidant properties of L. martabanica may provide a beneficial effect by protecting liver cells from damage caused by free radicals. Histopathology results revealed no liver cell necrosis and showed the regeneration of liver cells in the treatment group. L. martabanica extract did not cause changes in behavior, liver weight, hematological and biochemical profiles of the rats.

Volatile profiles from over-ripe purée of Thai mango varieties and their physiochemical properties during heat processing.

This research investigated volatile profiles of over-ripe Thai mango purée during thermal processing by solid-phase extraction, volatile quantification by XAD-2-solvent extraction, as well as descriptive sensory analysis. Overripe fruits of three varieties were analyzed for the ripening stage using specific gravity as well as firmness and the physiochemical properties were also reported. We found that aromatic profiles could be used as true representative to describe Thai mango identities of each varieties. A simple and straightforward heat treatment had differing effects on aroma characteristics and those effects were dependent with mango varieties. Indeed, the amount of terpene hydrocarbons and oxygenated sesquiterpenoids alternated after heat treatment. All descriptive attributes of heated 'sam-pee' purée were intensified while, heat treatment significantly improved only "mango identity" in 'maha-chanok' and "fermented" odour in 'keaw' purée. With or without heat treatment, the volatile profiles of 'maha-chanok' remained quite stable while heating played a significant role on chemical ingredients of 'keaw' and 'sam-pee'. Our study demonstrated that the manufacturing of the over-ripe mango into the products of high market value, selection of varieties is vitally important based upon their specific aroma characteristics before and after processing.

Mucuna pruriens (L.) DC. seed extract inhibits lipopolysaccharide-induced inflammatory responses in BV2 microglial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation caused by activated microglia is known to be associated with neurodegenerative diseases, e.g., Parkinson's disease (PD) and Alzheimer's disease (AD). Inhibiting the inflammatory process can be considered a potential strategy for the treatment of inflammation-associated diseases. Mucuna pruriens (L.) DC. (Leguminosae) has long been used in Thailand, India, China and other tropical countries to treat several diseases including PD. M. pruriens seeds have been found to possess a variety of pharmacological properties including antioxidant and anti-Parkinsonism effects. However, the anti-inflammatory effects of M. pruriens seeds during microglial activation have yet to be reported. AIM OF THE STUDY: The present study was performed to evaluate the anti-inflammatory effects of M. pruriens seed extract and elucidate its underlying mechanism using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. MATERIALS AND METHODS: BV2 microglial cells were pretreated with various concentrations of M. pruriens seed extract before being stimulated with LPS. The levels of inflammatory mediators were analyzed by Griess assay and enzyme-linked immunoassay (ELISA). The protein expression levels of inflammatory cytokines were determined by Western blot analysis. The translocation of nuclear factor-kappa B (NF-κB) was assessed by immunofluorescence microscopy. RESULTS: M. pruriens seed extract significantly inhibited the release of inflammatory mediators including nitric oxide (NO), IL-1ß, IL-6, and TNF-α in LPS-stimulated BV2 microglial cells. The extract also decreased the protein expression of IL-1ß, IL-6, and TNF-α. Moreover, M. pruriens seed extract inhibited the translocation of NF-κB. CONCLUSIONS: M. pruriens seed extract could suppress inflammatory responses in LPS-activated BV2 microglial cells by inhibiting the NF-κB signaling pathway. These findings support the use of M. pruriens seeds in traditional and alternative medicine for the treatment of PD and other inflammation-associated diseases.

Clinical Efficacy and Safety of Thai Herbal Formulation-6 in the Treatment of Symptomatic Osteoarthritis of the Knee: A Randomized-Controlled Trial.

BACKGROUND: Osteoarthritis of the knee is the most common form of arthritis. Identifying effective and safe herbal formulations that are locally available is viewed as a priority for sustainable development in a region. This study aimed to evaluate the efficacy and safety of Thai herbal formulation-6 (THF-6) in comparison with oral diclofenac in patients with moderate-to-severe osteoarthritis of the knee. METHODS: This randomized, double-blind, active-controlled, noninferiority trial randomly assigned patients with osteoarthritis of the knee to receive either THF-6 or diclofenac for four weeks. The primary outcome measure was the change from baseline in knee pain as measured by a 100 mm visual analog scale (VAS). Secondary outcome measures included knee stiffness, a stair climb test, the Knee Injury and Osteoarthritis Outcome Score, and safety parameters. Outcomes were assessed on a biweekly basis. Modified intention-to-treat (MITT) and perprotocol (PP) analyses were applied. RESULTS: A total of 200 patients were enrolled of whom 175 (87.5%) were included in the MITT analysis and 153 (76.5%) in the PP analysis. The mean change in VAS pain did not differ between the two groups, and the upper limit of the two-sided 95% confidence interval (CI) for comparison between the two groups was within the prespecified margin of 10 mm for noninferiority (MITT analysis: mean difference = 0.86, 95% CI = -4.39 to 6.10, p=0.748; PP analysis: mean difference = 1.98, 95% CI = -3.61 to 7.56, p=0.486). Significant improvement was observed in all the efficacy parameters in both groups. Dyspepsia was the most common adverse event: 23 patients in the THF-6 group and 28 in the diclofenac group (p=0.417). CONCLUSIONS: THF-6 offers an alternative to oral diclofenac for the short-term treatment of osteoarthritis of the knee. It was shown to be noninferior to oral diclofenac in relieving knee pain. This trial is registered with ChiCTR-IPR-15007213.

Clinical Efficacy and Safety of Yellow Oil Formulations 3 and 4 versus Indomethacin Solution in Patients with Symptomatic Osteoarthritis of the Knee: A Randomized Controlled Trial.

BACKGROUND: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of symptomatic osteoarthritis (OA) of the knee. However, searching for alternatives such as locally available medicinal herbs to manage OA knee pain remains of clinical value. The objective of the present study was to evaluate the efficacy and safety of two yellow oil formulations in patients with OA of the knee. METHODS: This prospective, randomized, single-blind, active-controlled, noninferiority study enrolled 102 patients with OA of the knee. Eligible patients were randomly assigned to apply either yellow oil formulation 3 (YOF3), yellow oil formulation 4 (YOF4), or indomethacin solution (INDO) topically four times daily for four weeks. Outcomes were assessed on a biweekly basis. The primary efficacy outcome measure was a 100 mm visual analog scale (VAS) of pain, while secondary endpoints included knee function, physical performance assessments, and safety parameters. Modified intention-to-treat and per-protocol analyses were applied. Assessment of noninferiority was done with a prespecified margin of 10 mm for VAS pain. RESULTS: Of 102 patients enrolled, 86 completed the study: 29/34 in the YOF3 group, 25/34 in the YOF4 group, and 32/34 in the INDO group. The absolute reduction in VAS pain at the final evaluation was -25.06 ± 13.91, -18.50 ± 16.06, and -23.38 ± 10.05 mm in the YOF3, YOF4, and INDO groups, respectively (p=0.169). Only YOF3 was found to be noninferior to INDO. Other efficacy outcomes were significantly improved in all three groups. All the interventions were well tolerated; no skin rash was observed in any of the three groups. CONCLUSIONS: YOF3 was shown to be noninferior to INDO in relieving knee pain and should be considered an alternative for the treatment of symptomatic OA of the knee. Further research into the mechanism of action of YOF3 and its long-term efficacy and safety is required.

Chemical Constituents, Antioxidant, Anti-MMPs, and Anti-Hyaluronidase Activities of Thunbergia laurifolia Lindl. Leaf Extracts for Skin Aging and Skin Damage Prevention.

This study aimed to investigate the potential usage of Thunbergia laurifolia Lindl. leaf extracts in the cosmetic industry. Matrix metalloproteinases (MMPs) and hyaluronidase inhibition of T. laurifolia leaf extracts, prepared using reflux extraction with deionized water (RE) and 80% v/v ethanol using Soxhlet's apparatus (SE), were determined. Rosmarinic acid, phenolics, and flavonoids contents were determined using high-performance liquid chromatography, Folin-Ciocalteu, and aluminum chloride colorimetric assays, respectively. Antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and linoleic acid-thiocyanate assays. MMP-1 inhibition was investigated using enzymatic and fluorescent reactions, whereas MMP-2, MMP-9, and hyaluronidase inhibition were investigated using gel electrophoresis. Cytotoxicity on human fibroblast cell line was also investigated. The results demonstrated that SE contained significantly higher content of rosmarinic acid (5.62% ± 0.01%) and flavonoids (417 ± 25 mg of quercetin/g of extract) but RE contained a significantly higher phenolics content (181 ± 1 mg of gallic acid/g of extract; p < 0.001). SE possessed higher lipid peroxidation inhibition but less DPPH• scavenging activity than RE. Both extracts possessed comparable hyaluronidase inhibition. SE was as potent an MMP-1 inhibitor as gallic acid (half maximal inhibitory concentration values were 12.0 ± 0.3 and 8.9 ± 0.4 mg/cm3, respectively). SE showed significantly higher MMP-2 and MMP-9 inhibition than RE (p < 0.05). Therefore, SE is a promising natural anti-ageing ingredient rich in rosmarinic acid and flavonoids with antioxidant, anti-hyaluronidase, and potent MMPs inhibitory effects that could be applied in the cosmetic industry.

Free Radical Scavenging Capability of Various Defatted Sesame Seed Cakes and Hulls Using EPR Compared with In Vitro Testing and HPLC Analysis.

The free radical scavenging activities of black and white sesame seed hulls and the powder of black and white sesame seed cakes were investigated using noninvasive continuous wave electron paramagnetic resonance (EPR) and antioxidant assays. With black sesame seed hulls and the powder of black sesame seed cakes, EPR detected the very strong single-line signal intensities that correspond to the stable organic radicals, while the spectrum of the white sesame seed hulls and the white sesame seed cakes showed no signal. The in vitro antioxidant activities of black and white sesame seed cake extract were evaluated by DPPH free radical scavenging activity, hydrogen peroxide scavenging activity, and ferric reducing antioxidant power (FRAP) assay. The results indicated that the extract from black sesame seed cake possessed a greater DPPH radical inhibitory activity and hydrogen peroxide inhibitory activity than white sesame seed cake extract, with IC50 values of 0.847 ± 0.011 mg/mL and 0.338 ± 0.007 mg/mL, respectively. Black sesame seed cake extract also showed a strong reducing power with a FRAP value of 1.307 ± 0.037 mM Fe (II)/g of extract weight and an EC1 value of 0.683 ± 0.002 mg/mL. The main compounds from the black and white sesame seed cake extracts were analysed using high-performance liquid chromatography (HPLC). The results revealed that the main compounds in black and white sesame seed cake extracts were in a group of water-soluble lignans, mainly sesaminol triglucoside and sesaminol diglucoside. However, sesaminol diglucoside was found in large amounts in the black sesame seed cake extract, while it was found in a very small amount in the white sesame seed cake extract. Therefore, these results demonstrated considerable antioxidant capacity of the sesame seed, especially in the black strain.

Acute effects of essential oil blend containing phlai oil on mood among healthy male volunteers: Randomized controlled trial.

Background Essential oil blend (ESOB) containing Zingiber montanum or Phlai and Zingiber tenuiscapus oils as the major components has high levels of terpenes such as sabinene, terpinene, terpinolene, and terpine-4-ol. Phlai is well known for its analgesic property, but its effects on mood remain unclear. This study aimed to investigate the acute effects of inhaling the ESOB containing phlai essential oils on mood and stress among healthy volunteers. Methods A prospective, randomized, double-blinded, controlled trial pilot study was conducted among 38 healthy male volunteers; 19 in the ESOB containing phlai oil group and 19 in the control group, which used olive oil. One single inhalation was provided continuously for 15 min via hot steam. Mood status was assessed pre- and post-intervention using the Visual Analog Scales for Mood, Anxiety, Stress and Alertness (MASA). Rorschach tests, in a modified analysis, were also employed. One-way ANCOVA was used to determine statistical differences of the mood test results between ESOB containing phlai oil and olive oil. Results Mean age of the participants was 22.11 (SD 2.1) years. Both ESOB containing phlai oil and olive oil increased the post-test scores of positive mood and reduced the scores of negative mood. However, no difference was observed regarding the mood test scores between groups, except concerning the Rorschach stress test (F (1,38)=6.486, p=0.015). The variance of change, explained by the model (R square), was 32.8%, while the adjusted R-squared was 0.290. Conclusions Single inhalation aromatherapy using ESOB containing phlai oil or olive oil showed an immediate improvement of mood states among healthy young male volunteers by easing the negative emotions and enhancing positive emotions, especially feelings of pleasure and contentment. Natural blend of phlai essential oils was more efficacious than olive oil in reducing emotional stress.