Cardamom seed bioactives: A review of agronomic factors, preparation, extraction and formulation methods based on emerging technologies to maximize spice aroma economic value and applications.

Cardamom seed (Elettaria cardamomum (L.)) is a well-appreciated spice in food and pharmaceutical industries owing to its unique rich flavor dominated by oxygenated monoterpenoids, α-terpinyl acetate and 1,8-cineole, to which most of the quality of cardamom essential oil (CEO) is attributed. CEO output is greatly influenced by different agronomic factors, processing, and EO extraction methods. In that context, the goal of this study is to provide an overarching review regarding emerged technologies along with their optimization parameters to achieve optimal oil yield with the best flavor quality. Furthermore, the recent approaches employed in CEO stabilization were highlighted alongside their pharmaceutical and food applications. Moreover, the different aspects of superlative CEO production including agricultural aspects, climatic requirements, and processing methods were also explained.

Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic.

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemotherapy and protect against chemotherapy-induced toxicity due to its scavenging properties. Furthermore, chemical compounds in cardamom, including limonene, cymene, pinene, linalool, borneol, cardamonin, indole-3-carbinol, and diindolylmethane, primarily target the programmed cell death lignin-1 gene, which is more prevalent in cancer cells than in healthy cells. This review provides the medicinal properties and pharmacological uses of cardamom, its cellular effects, and potential therapeutic uses in cancer prevention and treatment, as well as its use in reducing drug resistance and improving the overall health of cancer patients. Based on previous preclinical studies, cardamom shows significant potential as an anti-cancer agent, but further exploration for clinical use is warranted due to its diverse mechanisms of action.

A hybrid structure based on silk fibroin/PVA nanofibers and alginate/gum tragacanth hydrogel embedded with cardamom extract.

Hybrid structures made of natural-synthetic polymers have been interested due to high biological features combining promising physical-mechanical properties. In this research, a hybrid dressing consisting of a silk fibroin (SF)/polyvinyl alcohol (PVA) nanofibers and sodium alginate (SA)/gum tragacanth (GT) hydrogel incorporating cardamom extract as an antibacterial agent was prepared. Accordingly, SF was extracted from cocoons followed by electrospinning in blend form with PVA (SF/PVA ratio: 1:1) under the voltage of 18 kV and the distances of 15 cm. The SEM images confirmed the formation of uniform, bead free fibers with the average diameter of 199 ± 28 nm. FTIR and XRD results revealed the successful extraction of SF and preparation of mixed fibrous mats. Next, cardamom oil extract-loaded SA/GT hydrogel was prepared and the nanofibrous structure was placed on the surface of hydrogel. SEM analysis depicted the uniform morphology of hybrid structure with desirable matching between two layers. TGA analysis showed desired thermal stability. The swelling ratio was found to be 1251% after 24 h for the hybrid structure and the drug was released without any initial burst. MTT assay and cell attachment results showed favorable biocompatibility and cell proliferation on samples containing extract, and antibacterial activity values of 85.35% against S. aureus and 75% against E. coli were obtained as well. The results showed that the engineered hybrid nanofibrous-hydrogel film structure incorporating cardamom oil extract could be a promising candidate for wound healing applications and skin tissue engineering.

Cardamom consumption may improve cardiovascular metabolic biomarkers in adults: A systematic review and meta-analysis of randomized controlled trials.

The bioactive compounds in cardamom have been found to enhance cardiovascular health by improving blood lipids and inflammation. We hypothesized that cardamom consumption might ameliorate cardiovascular metabolic biomarkers in adults; however, there is still debate regarding its impact on cardiac metabolism. This research was therefore designed to determine if cardamom consumption had a favorable impact on lipid profiles, inflammatory markers, and oxidative stress indices as they related to cardiovascular diseases. A comprehensive search was conducted through PubMed, Scopus, Embase, Web of Science, and the Cochrane Library on July 4, 2023. Using a random-effects model pooled the weighted mean difference (WMD) and 95% confidence interval (CI). The final 12 trials containing 989 participants were included. The results illustrated that cardamom consumption could improve total cholesterol (WMD = -8.56 mg/dL; 95% CI, -14.90 to -2.22), triglycerides (WMD = -14.09 mg/dL; 95% CI, -24.01 to -4.17), high-sensitivity C-reactive protein (WMD = -1.01 ng/mL; 95% CI, -1.81 to -0.22), and interleukin-6 (WMD = -1.81 pg/mL; 95% CI, -3.06 to -0.56). However, it did not have significant influences on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and some indicators of oxidative stress. In conclusion, cardamom consumption can improve specific cardiovascular metabolic biomarkers and potentially confer protective effects on cardiovascular health. However, more large-scale clinical research with better designs would further validate the findings, which will offer substantial evidence of cardamom as nutritional and functional products.

The favorable impacts of cardamom on related complications of diabetes: A comprehensive literature systematic review.

BACKGROUND AND AIM: Complementary and alternative medicine plays an increasing role in preventing, and regulatory, complications associated with diabetes. There are plenty of polyphenolic compounds found in Elettaria cardamomum (Cardamom) such as luteolin, limonene, pelargonidin, caffeic acid, kaempferol, gallic acid, and quercetin which can be used in many metabolic diseases. METHOD: The objective of this systematic review was to appraise evidence from clinical and in vivo studies on the effects of cardamom on inflammation, blood glucose, oxidative stress and dyslipidemia of diabetes mellitus. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, the present study was carried out. Studies were conducted by searching databases such as EMBASE, Scopus, PubMed, Google Scholar, web of sciences, and Cochrane Library from the commencement until April 2022. RESULTS: All available human and animal studies examining the effects of cardamom on diabetes were published in the form of English articles. Finally, only 14 of the 241 articles met the criteria for analysis. Of the 14 articles, 8 were in vivo studies, and 6 were clinical trial studies. Most studies have indicated the beneficial effects of cardamom on insulin resistance, oxidative stress and inflammation. Cardamom also improved dyslipidemia, but had no substantial effect on weight loss. CONCLUSION: According to most studies, cardamom supplementation enhanced antioxidant enzyme production and activity in diabetes mellitus and decreased oxidative stress and inflammatory factors. Despite this, the exact mechanism of the disease needs to be identified through more clinical trials.

Black cardamom (Amomum subulatum) extract improves growth potential, antioxidant status, immune parameters and response to crowding stress in Catla catla.

Natural herbs are excellent alternatives to synthetic compounds to enhance the growth performance and health status of fish. This study was conducted to evaluate the efficacy of black cardamom (Amomum subulatum) extract (BCE) as an herbal supplement in improving the growth, antioxidant status, haematology, and serum biochemistry of Catla catla. The acclimatized fish (N = 900; average initial weight = 14.44 ± 0.33 g) were allocated into five groups (60 fish/group in triplicate) in hapas (4 × 2 × 2.5 ft) and provided with feed containing 0 (control), 0.5, 1, 2 and 4 g/kg BCE for 90 days before being subjected to 8 days of crowding stress. After 90 days, significantly higher feed utilization and growth were observed in all BCE-fed treatments compared to the control; however, the maximum values of these parameters were noted in the 2 g/kg BCE-fed treatment. Moreover, the BCE-fed groups exhibited a significant increase in antioxidant indices (glutathione peroxidase, superoxide dismutase and catalase), with a significant reduction in malondialdehyde levels, indicating a higher antioxidant capacity compared to the control. Significant improvements in haematological parameters, such as an increase in haematocrit, haemoglobin and red blood cells and a decrease in white blood cells, were observed in BCE-fed treatments compared to the control. Furthermore, BCE-fed groups showed a significant decrease in serum glucose, cortisol and triglycerides, while total protein, globulin and albumin levels were significantly higher compared with the control. During the feeding trial of 90 days, no mortality was observed; however, the lowest cumulative mortality was noted in the 2 g/kg BCE group after crowding stress of 8 days. In conclusion, the use of BCE in feed can enhance the growth performance, antioxidant status, haematology, and serum biochemistry of C. catla and improve the resistance against crowding stress. The optimum levels of BCE for C. catla were estimated based on weight gain % (1.78 g/kg; R2 = 0.97), feed conversion ratio (1.65 g/kg; R2 = 0.98), MDA content (1.66 g/kg; R2 = 0.93) and serum lysozyme activity (1.72 g/kg; R2 = 1) using broken-line regression analysis.

Elevation determines the productivity of large cardamom (Amomum subulatum Roxb.) cultivars in Sikkim Himalaya.

Large cardamom (Amomum subulatum Roxb.) is an economically important cash crop that provides a livelihood option for the rural communities in Sikkim Himalaya. However, its production has declined drastically over the past few decades due to climate change and other factors affecting the livelihood of marginal cardamom-dependent farmers in the region. Climate change causes a shift in elevational distributions of mountain species, and it is pivotal to understand its effect on yield and yield-related traits for economically important plant species like large cardamom. For this, we randomly studied 41 large cardamom cultivation sites in Sikkim (India) with elevations ranging between 975 and 2069 m asl and evaluated the yield-related traits (number of capsules per spike, capsule length, capsule width, fresh capsule weight, dry capsule weight, number of seeds per locule, fresh seed weight, and dry seed weight) in five cultivars (Dzongu Golsey, Sawney, Seremna, Ramsey, and Varlangey). We observed a significant variability (P < 0.05) for morphometric traits in each of the five cultivars cultivated in different elevations. The cultivation of low-elevation cultivars like Seremna and Dzongu Golsey (suitable in elevation < 975 m) has shifted upward to mid (975-1515 m) and high-elevation (> 1515 m), while cultivation of high-elevation Ramsey cultivar (suitable in elevation > 1515 m) has shifted downward (< 1515 m). The Dzongu Golsey, Sawney, and Seremna cultivated in mid-elevation (975-1515 m) performed better in terms of yield-related traits than the same cultivars cultivated in high-elevation (> 1515 m) and showed moderate to high negative correlation between elevation and yield-related traits, indicating the negative effect of elevation on their yield. Likewise, Ramsey and Varlangey cultivated in high elevation (> 1515 m) performed better than the one cultivated in mid-elevation (975-1515 m) and depicted moderate to high positive correlation between elevation and yield-related traits, suggesting a positive influence of elevation on their yield. Although there is an elevational shift in the cultivation of large cardamom cultivars, the elevation influences the performance of the large cardamom cultivars, and it also suggests cultivating the cultivars in their suitable elevation range for better productivity.

Extraction of Active Compounds from Mixtures of Hemp (Cannabis sativa) with Plants of the Zingiberaceae Family.

Hemp is probably one of the most studied plants for its health-promoting properties, with countless documented and patented extraction methods, but literature is scarce on the simultaneous extraction of mixture of raw materials. Hemp, along with other plant materials, could represent a potentially highly valuable source material with resulting reciprocal effects. In this study, hemp (Cannabis sativa) and three members of the Zingiberaceae family, ginger (Zingiber officinale), turmeric (Curcuma longa), and cardamom (Elettaria cardamomum), were extracted simultaneously, and their bioactive component values were investigated. Two extraction methods were used, namely ultrasound-assisted extraction with ethanol and supercritical fluid extraction with carbon dioxide. First, extracts were obtained from separate plant materials. Then, hemp was extracted in combination with ginger, turmeric, and cardamom in a 1:1 ratio. The extracts obtained were evaluated for their antioxidant activity and total phenolic content using UV/VIS spectrophotometry; cannabinoid content, 6-gingerol, and 6-shogaol were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); volatile components such as 1,8-cineole, alpha-terpinyl acetate, linalool, and aR-turmerone were measured using gas chromatography with mass spectrometry (GC/MS).

Exploring the potential of 1,8-cineole from cardamom oil against food-borne pathogens: Antibacterial mechanisms and its application in meat preservation.

Food-borne pathogenic bacteria are a major public health concern globally. Traditional control methods using antibiotics have limitations, leading to the exploration of alternative strategies. Essential oils such as cardamom possess antimicrobial properties and have shown efficacy against food-borne pathogenic bacteria. The utilization of essential oils and their bioactive constituents in food preservation is a viable strategy to prolong the shelf-life of food products while ensuring their quality and safety. To the best of our knowledge, there are no studies that have utilized 1,8-cineole (the main active constituent of cardamom essential oil) as a preservative in meat, so this study might be the first to utilize 1,8-cineole as an antibacterial agent in meat preservation. The application of 1,8-cineole had a significant suppressive impact on the growth rate of Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Salmonella Typhimurium in meat samples stored for 7 days at 4 °C. Additionally, the surface color of the meat samples was not negatively impacted by the application of 1,8-cineole. The minimum inhibitory concentration was 12.5-25 mg/ml, and the minimum bactericidal concentration was 25-50.0 mg/ml. The bacterial cell membrane may be the target of cardamom, causing leakage of intracellular proteins, ATP, and DNA. The obtained data in this study may pave a new avenue for using 1,8-cineole as a new perspective for dealing with this problem of food-borne pathogens and food preservation, such as meat.

Antileishmanial effects, cellular mechanisms, and cytotoxicity of Elettaria cardamomum essential oil against Leishmania major infection.

Leishmaniasis is an infectious disease with various clinical manifestations. We studied the therapeutic effects of Elettaria cardamomum essential oil (ECEO) against Leishmania major infection. In vitro effects of ECEO against L. major were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and macrophage assays. Nitric oxide (NO) production, infection inhibition in macrophages, and the apoptotic activity of ECEO in treated parasites were also measured. By calculating the 50% cytotoxic concentrations (CC50), we studied the cytotoxicity effects of ECEO on human macrophage cells (THP-1). The efficacy of ECEO for improving cutaneous leishmaniasis (CL) lesions in mice (BALB/c) was determined by evaluating the size of lesions and the number of amastigotes before and after four weeks of treatment. The effects of ECEO on liver and kidney function in the tested mice were also evaluated. ECEO dose-dependently (p<0.001) inhibited the viability and the mean number of promastigotes and amastigote forms of L. tropica. Four weeks of treatment with ECEO at the doses of 2.5 and 5 mg/kg/ day significantly (p<0.001) improved the CL lesions and reduced the number of parasites in the infected mice. ECEO significantly increased NO production, apoptosis induction, and infection rate in parasites. The CC50 value for ECEO and MA was 303.4 µg/mL and 835.2 µg/mL, respectively. In the mice receiving ECEO at the doses of 2.5 and 5 mg/kg/day for 28 days, no significant change was reported between the serum level of liver enzymes and kidney factors when compared with the control group. ECEO displayed promising efficacy in parasite reduction in vitro and in the animal model. ECEO can thus be used as an alternative medicine to treat CL.

Non-cytotoxic, highly functionalized cellulose nanocrystals with high crystallinity and thermal stability derived from a novel agromass of Elettaria cardamomum, using a soft and benign mild oxalic acid hydrolysis.

Non-cytotoxic, highly crystalline, and functionalized, thermally stable cellulose nanocrystals are extracted from the stems of Elettaria cardamom, a novel underutilised agromass, by employing a neat green, mild oxalic acid hydrolysis. The protocol involves a chemo-mechanical strategy of coupling hydrolysis with steam explosion and homogenization. The obtained CNC showed a crystallinity index of 81.51 %, an aspect ratio of 17.80 ± 1.03 and a high degradation temperature of about 339.07 °C. The extraction procedure imparted a high negative surface functionalization with a zeta potential value of -34.244 ± 0.496 mV and a polydispersity of 16.5 %. The CNC had no antibacterial activity, according to non-cytotoxic experiments conducted on four bacterial strains. This supports the notion of "One Health" in the context of AMR by demonstrating the safety of antibiotic resistance due to consistent exposure upon environmental disposal. The as-extracted nanocellulose crystals can be a potential candidate for commercial application in wide and diversified disciplines like food packaging, anti-infective surfaces for medical devices, biosensors, bioelectronics etc.

Effect of Elettaria cardamomum L. on hormonal changes and spermatogenesis in the propylthiouracil-induced hypothyroidism male BALB/c mice.

INTRODUCTION: Spermatogenesis is significantly influenced by the thyroid gland. Thyroid disorders can be caused by a variety of factors. Traditionally, Ellettaria cardamomum has been used to treat a variety of ailments. The effects of E. cardamomum extract (ECE) on spermatogenesis in hypothyroid mice were investigated in this study. METHODS: In this study 42 male mice, weighing (25-35 g) were randomly divided in six groups: control group (taking normal saline, 0.5 mL/day, by oral gavage [P.O.]), hypothyroid group (taking 0.1% propylthiouracil in drinking water for 2 weeks), hypothyroid groups treated by levothyroxine (15 mg/kg/day, P.O.) and hypothyroid groups treated by ECE (100, 200 and 400 mg/kg/day, P.O.). After the end of experiments the mice were anaesthetised and blood samples were collected for hormonal analysis. RESULTS: The sperm count and microscopic studies of testes were done also. Our results showed that the T3 , T4 , testosterone levels and spermatogenesis in hypothyroid animals decreased and thyroid-stimulating hormone, follicle-stimulating hormone and luteinizing hormone increased compared with control group. Treatment by ECE reverse these effects in comparison with hypothyroid group. CONCLUSIONS: According to our findings, the ECE may stimulates thyroid gland function and increases testosterone and spermatogenesis.

Protective Role of Phenolic Compounds from Whole Cardamom (Elettaria cardamomum (L.) Maton) against LPS-Induced Inflammation in Colon and Macrophage Cells.

The chemical profiling of phenolic and terpenoid compounds in whole cardamom, skin, and seeds (Elettaria cardamomum (L.) Maton) showed 11 phenolics and 16 terpenoids, many of which are reported for the first time. Herein, we report the anti-inflammatory properties of a methanolic extract of whole cardamom in colon and macrophage cells stimulated with an inflammatory bacteria lipopolysaccharide (LPS). The results show that cardamom extracts lowered the expression of pro-inflammatory genes NFkß, TNFα, IL-6, and COX2 in colon cells by reducing reactive oxygen species (ROS) while not affecting LXRα. In macrophages, cardamom extracts lowered the expression of pro-inflammatory genes NFkß, TNFα, IL-6, and COX2 and decreased NO levels through a reduction in ROS and enhanced gene expression of nuclear receptors LXRα and PPARγ. The cardamom extracts in a range of 200-800 µg/mL did not show toxicity effects in colon or macrophage cells. The whole-cardamom methanolic extracts contained high levels of phenolics compounds (e.g., protocatechuic acid, caffeic acid, syringic acid, and 5-O-caffeoylquinic acid, among others) and are likely responsible for the anti-inflammatory and multifunctional effects observed in this study. The generated information suggests that cardamom may play a protective role against low-grade inflammation that can be the basis of future in vivo studies using mice models of inflammation and associated chronic diseases.

Protective effect of ethanolic extract of Elettaria Cardamomum against gentamicin hepato-renal toxicity in male albino rats.

OBJECTIVE: Cardamom is one of the spices containing a wide range of antioxidants and is used in medicinal preparations. Thus, in this study, we want to explore the protective effect of ethanolic cardamom extract on the liver-kidney toxicity caused by gentamicin in male albino rats. MATERIALS AND METHODS: The experiment was applied to twenty-eight male albino rats divided randomly into four groups. The control group was given 1 ml/kg of saline orally. The gentamicin (GM) group was given a daily 80 mg/kg i.p of GM for seven days. Another group was given 100 or 200 mg/kg b.wt. p.o. ethanolic extract of Elettaria Cardamomum (EC) for seven days. Blood and liver-kidney samples were taken after the end of the study for analyses to test for liver-kidney function and lipid profile (LP). RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin activities were higher in the GM group than in the control group. However, the groups' differences in globulin levels and total protein (TP) were not statistically significant. Compared to the control group, the albumin level in the gentamicin group was considerably lower. On the other hand, creatinine and urea levels, lipid, serum total cholesterol levels, and high-density lipoprotein (HDL) significantly increased in the gentamicin group but decreased in the control group and co-treated groups with gentamicin and ethanolic extract EC. Low-density lipoprotein (LDL) significantly dropped, while the control group showed high levels of lipid and serum total cholesterol. CONCLUSIONS: EC ethanolic extract shields the liver-kidney against GM harmful effects in male rats. Recent research demonstrated that the effects of the plant cardamom were the same at both low-high doses. The phenolic elements in EC may be responsible for this protective effect.

Aflatoxin B1 Detoxification Potentials of Garlic, Ginger, Cardamom, Black Cumin, and Sautéing in Ground Spice Mix Red Pepper Products.

The uses of natural plant origin bioactive compounds are emerging as a promising strategy to detoxify aflatoxin B1 (AFB1). This study aimed to explore the potential of cooking, phytochemicals content, and antioxidant activities derived from garlic, ginger, cardamom, and black cumin to detoxify AFB1 on spice mix red pepper powder (berbere) and sauté. The effectiveness of the samples was analyzed for AFB1 detoxification potential through standard methods for the examination of food and food additives. These major spices showed an AFB1 level below the detection limit. After cooking in hot water for 7 min at 85 ℃, the experimental and commercial spice mix red pepper showed the maximum AFB1 detoxification (62.13% and 65.95%, respectively). Thus, mixing major spices to produce a spice mix red pepper powder had a positive effect on AFB1 detoxification in raw and cooked spice mix red pepper samples. Total phenolic content, total flavonoid content, 2,2-diphenyl-1-picrylhydrazyl, ferric ion reducing antioxidant power, and ferrous ion chelating activity revealed good positive correlation with AFB1 detoxification at p < 0.05. The findings of this study could contribute to mitigation plans of AFB1 in spice-processing enterprises. Further study is required on the mechanism of AFB1 detoxification and safety of the detoxified products.

Antioxidant Activity in Extracts from Zingiberaceae Family: Cardamom, Turmeric, and Ginger.

An increase in life expectancy leads to a greater impact of chronic non-communicable diseases. This is even more remarkable in elder populations, to whom these become main determinants of health status, affecting mental and physical health, quality of life, and autonomy. Disease appearance is closely related to the levels of cellular oxidation, pointing out the importance of including foods in one's diet that can prevent oxidative stress. Previous studies and clinical data suggest that some plant-based products can slow and reduce the cellular degradation associated with aging and age-related diseases. Many plants from one family present several applications that range from the food to the pharmaceutical industry due to their characteristic flavor and scents. The Zingiberaceae family, which includes cardamom, turmeric, and ginger, has bioactive compounds with antioxidant activities. They also have anti-inflammatory, antimicrobial, anticancer, and antiemetic activities and properties that help prevent cardiovascular and neurodegenerative diseases. These products are abundant sources of chemical substances, such as alkaloids, carbohydrates, proteins, phenolic acids, flavonoids, and diarylheptanoids. The main bioactive compounds found in this family (cardamom, turmeric, and ginger) are 1,8-cineole, α-terpinyl acetate, ß-turmerone, and α-zingiberene. The present review gathers evidence surrounding the effects of dietary intake of extracts of the Zingiberaceae family and their underlying mechanisms of action. These extracts could be an adjuvant treatment for oxidative-stress-related pathologies. However, the bioavailability of these compounds needs to be optimized, and further research is needed to determine appropriate concentrations and their antioxidant effects in the body.

Cardamom (Elettaria cardamomum (L.) Maton) Seeds Intake Increases Energy Expenditure and Reduces Fat Mass in Mice by Modulating Neural Circuits That Regulate Adipose Tissue Lipolysis and Mitochondrial Oxidative Metabolism in Liver and Skeletal Muscle.

Cardamom seed (Elettaria cardamomum (L.) Maton; EC) is consumed in several countries worldwide and is considered a nutraceutical spice since it exerts antioxidant, anti-inflammatory, and metabolic activities. In obese individuals, EC intake also favors weight loss. However, the mechanism for these effects has not been studied. Here, we identified that EC modulates the neuroendocrine axis that regulates food intake, body weight, mitochondrial activity, and energy expenditure in mice. We fed C57BL/6 mice with diets containing 3%, 6%, or 12% EC or a control diet for 14 weeks. Mice fed the EC-containing diets gained less weight than control, despite slightly higher food intake. The lower final weight of EC-fed mice was due to lesser fat content but increased lean mass than control. EC intake increased lipolysis in subcutaneous adipose tissue, and reduced adipocyte size in subcutaneous, visceral, and brown adipose tissues. EC intake also prevented lipid droplet accumulation and increased mitochondrial content in skeletal muscle and liver. Accordingly, fasting and postprandial oxygen consumption, as well as fasting fat oxidation and postprandial glucose utilization were higher in mice fed with EC than in control. EC intake reduced proopiomelanocortin (POMC) mRNA content in the hypothalamic arcuate nucleus, without an impact on neuropeptide Y (NPY) mRNA. These neuropeptides control food intake but also influence the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes. Thyrotropin-releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and circulating triiodothyronine (T3) were lower in EC-fed mice than in control. This effect was linked with decreased circulating corticosterone and weight of adrenal glands. Our results indicate that EC modulates appetite, increases lipolysis in adipose tissue and mitochondrial oxidative metabolism in liver and skeletal muscle, leading to increased energy expenditure and lower body fat mass. These metabolic effects were ascribable to the modulation of the HPT and HPA axes. LC-MS profiling of EC found 11 phenolic compounds among which protocatechuic acid (23.8%), caffeic acid (21.06%) and syringic acid (29.25%) were the most abundant, while GC-MS profiling showed 16 terpenoids among which costunolide (68.11%), ambrial (5.3%) and cis-α-terpineol (7.99%) were identified. Extrapolation of mice-to-human EC intake was performed using the body surface area normalization equation which gave a conversion equivalent daily human intake dose of 76.9-308.4 mg bioactives for an adult of 60 kg that can be obtained from 14.5-58.3 g of cardamom seeds (18.5-74.2 g cardamom pods). These results support further exploration of EC as a coadjuvant in clinical practice.

Antioxidant Activity and GC-MS Profile of Cardamom (Elettaria cardamomum) Essential Oil Obtained by a Combined Extraction Method-Instant Controlled Pressure Drop Technology Coupled with Sonication.

Cardamom Essential oils are highly demanded because of their antimicrobial, anti-inflammatory, and antioxidant activities. Nonetheless, retrieving quality extracts quickly with efficient energy savings has been challenging. Therefore, green technologies are emerging as possible alternatives. Thus, this study evaluates the yield and quality of the instant controlled pressure drop (DIC) process coupled with ultrasound-assisted extraction (UAE) of cardamom essential oil (CEO). Likewise, the antioxidant activity, chemical profile of CEO, and microstructure of seeds were analyzed. This study analyzed 13 different treatments with varying saturated steam processing temperatures (SSPT), thermal processing times (TPT), and 1 control. The results showed that CEO yield increased significantly by DIC (140 °C and 30 s) and UAE compared to the control (22.53% vs. 15.6%). DIC 2 (165 °C, 30 s) showed the highest DPPH inhibition (79.48%) and the best Trolox equivalent antioxidant capacity (TEAC) by the control with 0.60 uMTE/g. The GC/MS analysis showed 28 volatile constituents, withα-Terpinyl acetate, geranyl oleate, and oleic acid being the most abundant. DIC (140 °C and 30 s) and UAE showed the best yield and chemical profile. The SEM microscopy of untreated seeds revealed collapsed structures before the oil cell layer, which reduced the extraction yield, contrary to DIC-treated seeds, with more porous structures. Therefore, combining innovative extraction methods could solve the drawbacks of traditional extraction methods.

Cardamom oil ameliorates behavioral and neuropathological disorders in a rat model of depression induced by reserpine.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is a public health problem. Despite the availability of treatment options, its prevalence is increasing. A high rate of treatment failure is often reported, along with considerable side effects associated with synthetic antidepressants. Therefore, developing effective and safe antidepressants from traditional herbs or natural products as an alternative strategy is warranted to avoid side effects and increase drug efficacy. In traditional medicine, cardamom has traditionally been used to treat conditions like asthma, tooth and gum infections, cataracts, nausea, diarrhea, and even depression and anxiety as well as some problems with the heart, kidneys, and digestive system. AIM OF THE STUDY: The current study aimed to evaluate the antidepressant activity of cardamom oil in a rat model of depression induced by reserpine and compare it with the activity of the antidepressant drug fluoxetine. MATERIALS AND METHODS: Depression-like symptoms were induced in male rats by daily i. p. injection of reserpine (0.2 mg/kg/d for 15 d followed by 0.1 mg/kg/d for 21 d to maintain the depressive state), and the rats were treated with cardamom oil (oral dose = 200 mg/kg/d) for 21 d along with the maintenance dose of reserpine. We performed behavioral tests (forced swimming test and open-field test) and evaluated biochemical markers of depression. RESULTS: Our findings revealed that cardamom oil attenuated depression-like symptoms in reserpine-injected rats by improving the behavioral changes measured by the forced swimming test and the locomotor activities measured by the open-field test. In reserpine-injected rats, cardamom oil exerted antidepressant-like effects by modulating lower levels of brain monoamine neurotransmitters (serotonin, norepinephrine, and dopamine), GSH, and higher oxido-nitrosative stress parameters (malondialdehyde and nitric oxide). Moreover, cardamom oil alleviated depression-like behaviors by lowering monoamine oxidase activity and raising the activities of Na+/K+-ATPase and acetylcholinesterase and levels of a brain-derived neurotrophic factor in the cortex and hippocampus. CONCLUSION: We recommend the use of cardamom oil as a safe and reliable treatment or an adjuvant for preventing depression-like symptoms in patients suffering from depression.

Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial.

BACKGROUND: Standard-of-care treatment for patients with newly diagnosed multiple myeloma is bortezomib-based induction followed by high-dose melphalan and autologous haematopoietic stem-cell transplantation (HSCT) and lenalidomide maintenance. We aimed to evaluate whether an immunomodulatory-free carfilzomib-based induction, consolidation, and maintenance protocol without autologous HSCT was non-inferior to the same induction regimen followed by autologous HSCT and maintenance. METHODS: CARDAMON is a randomised, open-label, phase 2 trial in 19 hospitals in England and Wales, UK. Newly diagnosed, transplantation-eligible patients with multiple myeloma aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 received four 28-day cycles of carfilzomib (56 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), cyclophosphamide (500 mg orally on days 1, 8, and 15), and dexamethasone (40 mg orally on days 1, 8, 15, and 22; KCd), followed by peripheral blood stem cell mobilisation. Patients with at least a partial response were randomly assigned (1:1) to either high-dose melphalan and autologous HSCT or four cycles of KCd. All randomised patients received 18 cycles of carfilzomib maintenance (56 mg/m2 intravenously on days 1, 8, and 15). The primary outcomes were the proportion of patients with at least a very good partial response after induction and difference in progression-free survival rate at 2 years from randomisation (non-inferiority margin 10%), both assessed by intention to treat. Safety was assessed in all patients who started treatment. The trial is registered with ClinicalTrials.gov (NCT02315716); recruitment is complete and all patients are in follow-up. FINDINGS: Between June 16, 2015, and July 8, 2019, 281 patients were enrolled, with 218 proceeding to randomisation (109 assigned to the KCd consolidation group [99 of whom completed consolidation] and 109 to the HSCT group [104 of whom underwent transplantation]). A further seven patients withdrew before initiation of carfilzomib maintenance (two in the KCd consolidation group vs five in the HSCT group). Median age was 59 years (IQR 52 to 64); 166 (59%) of 281 patients were male and 115 (41%) were female. 152 (71%) of 214 patients with known ethnicity were White, 37 (17%) were Black, 18 (8%) were Asian, 5 (2%) identified as Mixed, and 2 (1%) identified as other. Median follow-up from randomisation was 40·2 months (IQR 32·7 to 51·8). After induction, 162 (57·7%; 95% CI 51·6 to 63·5) of 281 patients had at least a very good partial response. The 2-year progression-free survival was 75% (95% CI 65 to 82) in the HSCT group versus 68% (95% CI 58 to 76) in the KCd group (difference -7·2%, 70% CI -11·1 to -2·8), exceeding the non-inferiority margin. The most common grade 3-4 events during KCd induction and consolidation were lymphocytopenia (72 [26%] of 278 patients who started induction; 15 [14%] of 109 patients who started consolidation) and infection (50 [18%] of 278 for induction; 15 [14%] of 109 for consolidation), and during carfilzomib maintenance were hypertension (20 [21%] of 97 patients in the KCd consolidation group vs 23 [23%] of 99 patients in the HSCT group) and infection (16 [16%] of 97 patients vs 25 [25%] of 99). Treatment-related serious adverse events at any point during the trial were reported in 109 (39%) of 278 patients who started induction, with infections (80 [29%]) being the most common. Treatment-emergent deaths were reported in five (2%) of 278 patients during induction (three from infection, one from cardiac event, and one from renal failure) and one of 99 patients during maintenance after autologous HSCT (oesophageal carcinoma). INTERPRETATION: KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggests that further studies are warranted to explore deferred autologous HSCT in some subgroups, such as individuals who are MRD negative after induction. FUNDING: Cancer Research UK and Amgen.