Jundishapur Journal of Natural Pharmaceutical Products
Volume:18 Issue: 1, Feb 2023

Cardiovascular disorders are a leading cause of mortality and morbidity worldwide, especially in people with diabetes. Due to synthetic drugs’ adverse effects, new medicines are needed.

Iranian traditional medicine (ITM) is one of the oldest medical systems. In this article, we first introduce a list of cardiotonic medicinal plants based on ITM. Then we review the cardio-related effects of these plants based on electronic databases.

Among the introduced medicinal plants from ITM, Phyllanthus emblica L., Rosa canina L., Ocimum basilicum L., and Melissa officinalis L. have cardiotonic effects. Also, P. emblica, O. basilicum, M. officinalis, Citrus medica L., Malus domestica Borkh., Elettaria cardamomum (L.) Maton, and R. canina have cardioprotective effects and possess several biological activities that reduce cardiovascular disease risk factors.

The cardiotonic medicinal plants based on ITM have excellent value; several pharmacological studies have proved some of their cardioprotective and cardiotonic effects. The other plants’ potential for improving the heart’s contractile power as a cardiotonic drug must be evaluated in further pharmacological and clinical studies.

Peptides are highly potent, selective, and relatively safe therapeutics. Over the past two decades, natural peptides have been obtained, studied, and eventually approved by the Food and Drug Administration (FDA) due to advancements in identification, production, modification, and analytical technologies. Some peptide therapeutics has been derived from the venom gland of venomous animals, including snake, leech, lizard, snail, and scorpion. Scorpion was identified as a reservoir of important peptides with pharmaceutical properties. The scorpion uses these peptides for capturing prey and defense. However, their pharmacological properties in treating different diseases, including cardiac problems, autoimmune and infectious diseases, and diverse cancers, have been confirmed. Ion channel modifiers are the greatest components of the scorpion venom glands. Due to advances in proteomic and transcriptomic approaches, the identification of new scorpion venom peptides is steadily increasing. In this review, we tried to represent the current status of peptide medicines and describe the last peptide medications approved by FDA in 2022. Moreover, we will further explain potent peptides originating from scorpion venom, which have gone through important steps to be approved.

To date, more than 300,000 distinct peptides have been identified in scorpion venom. However, only a limited number of these peptides have been described.

We characterized some putative peptides from the venom gland cDNA library of the Iranian yellow scorpion Hemiscorpius lepturus.

Total RNA was extracted from yellow Iranian scorpion glands. Single-stranded cDNA (sscDNA) and double-stranded cDNA (dscDNA) were synthesized by polymerase chain reaction (PCR). A cDNA library was achieved by inserting dscDNA into a special vector and subsequently transformed to chemically competent Escherichia coli as a host. The library was screened by culturing the liquid library on Lysogeny broth (LB)-agar plates. Analysis of positive clones was performed by plasmid extraction and the sequencing of the inserts. Finally, all cDNA sequences were analyzed and characterized by bioinformatics software.

One hundred colonies were randomly analyzed. Eighty-nine cDNA sequences had acceptable quality for bioinformatics analysis. Five sequences were selected for further analysis. The peptides related to these sequences were divided into two groups, non-disulfide bridge peptides (NDBP) and disulfide bridge peptides (DBP), the application of which in health and medical issues has been suggested.

The data obtained in this study may be an important resource for further in vivo and in vitro functional assays to identify valuable therapeutic peptides.

Eryngium is a genus with 274 species, which belongs to the Umbelliferae family. The nine species of this genus are endemic to Iran. The existence of terpenoids, saponins, flavonoids, and steroid components in most Eryngium species is the reason behind their anti-inflammatory, anti-cancer, and especially, anti-diabetic effects among the well-known medicinal plants.

This study aimed to evaluate the effects of anti-diabetic features of Eryngium thyrsoideum and caucasicum on streptozotocin (STZ)-induced diabetic mice.

The extract of the plants’ dried samples was prepared by using 70% ethanol solvent and adopting the maceration method. The mice were divided into eight groups, and the mice with a high blood glucose of more than 200 mg/dL were assigned to diabetic groups. Diabetic animals received different doses of the extract orally or through intraperitoneal (IP) injection for eighteen days. The animals were anesthetized by IP injection of ketamine and xylazine, and serum samples were isolated.

The results showed that hydroalcoholic extract of E. thyrsoideum significantly reduced the blood sugar level in diabetic groups receiving the extract (oral and IP) in low (100 mg/kg) and high (300 mg/kg) doses. Overall, oral glucose tolerance decreased significantly after two hours. Coincidental management of STZ and 300 mg/kg of the extract consumed orally reduced the blood sugar level remarkably. Serum malondialdehyde (MDA) and serum insulin levels significantly decreased and increased, respectively, in the diabetic groups receiving low and high doses (oral and IP) of the E. thyrsoideum extract. In the case of E. caucasicum, no significant effect in terms of reducing blood sugar and other factors was observed.

In sum, receiving 100 mg/kg and 300 mg/kg of hydroalcoholic extract (oral and IP) decreased the blood sugar level, while receiving oral glucose tolerance, serum MDA, and serum insulin caused a significant increase.

Pinus eldarica contains various components such as phenolic and terpene materials. Previous reports showed these two components had anti-insect properties. Pest control, especially for different species of cockroaches, is important because of transmission of various diseases.

The aim of this study was to determine the anti-insect potential of P. eldarica leaf essential oil (PLE) against Blattella germanica, German cockroach.

The anti-insect activity of different doses (50, 150, and 300 μg/mL) of PLE of two areas of clean air (CA) zones and polluted air (PA) zones was evaluated by contact toxicity, fumigant toxicity, and repellence tests.

The results of contact test showed that the percentages of mortality rates were increased significantly in a dose- and time-dependent manner in both contact and fumigation methods as well as repellency percentage. Also, the results related to PA zones were more significant than CA zones.

This study showed that essential leaf oil of P. eldarica induced mortality and repellency in German cockroach, and it can probably be used as a good candidate for pest control, in particular cockroaches.

The application of natural antimicrobial and antioxidant agents in food and pharmaceutical products has recently become a trend due to the high demand for them from consumers. Postbiotics are bioactive compounds that are produced when the healthy bacteria in the gut ferment fiber.

This study aimed to compare the antibacterial and antioxidant properties of postbiotics from 5 different lactic acid bacteria (LAB) including Lactiplantibacillus fermentum, Lactiplantibacillus plantarum, Lactiplantibacillus rhamnosus, Lactobacillus casei, and Lactobacillus acidophilus.

Two different methods were adopted to obtain postbiotics (M1 and M2). M1 was the simple method in which the centrifugation was employed while in M2 method, ethyl acetate was used to obtain postbiotics. Agar disc diffusion, minimum inhibition concentration, and minimum bactericidal concentration were used to assess the antimicrobial activity of postbiotics. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was performed in order for investigating the antioxidant property.

The best results were recorded for L. casei compared to other LABs. Highest values of the agar disc diffusion method were obtained for L. casei. The inhibition zones for Salmonella enterica, Listeria monocytogenes, and Staphylococcus aureus, for examples, were 22 mm, 20 mm, and 19 mm, respectively. The postbiotic of L. casei also exhibited the most potent antioxidant activity among other probiotic bacteria. The data showed that M2 was a more effective method than the other method for acquiring postbiotics.

It was recommended LABs postbiotics should be applied as antioxidant, antimicrobial, and preservatives in food and pharmaceutical industries due to their desired effects and natural characteristics.

The chemical agents applied to reduce the complications of hydatid cyst surgery are not free of side effects. Formononetin (FMN), as a natural isoflavone, has been shown to have various therapeutic benefits.

We studied the in vitro and ex vivo protoscolicidal activity and cellular mechanisms of FMN against hydatid cyst protoscoleces.

Formononetin at 75, 150, and 300 μg/mL was mixed with hydatid cyst protoscoleces (103/mL), and the viability was determined in 5 to 60 min through eosin staining assay. The effect of FMN on caspase-3 activity was tested through a commercial colorimetric protease kit. In addition, the penetrability of the plasma membrane of protoscoleces after exposure to FMN was also determined by the SYTOX assay.

Formononetin at 300 μg/mL completely destroyed hydatid cyst protoscoleces after 30 minutes. While at 150 μg/mL, after 60 minutes of contact, 100% of protoscoleces were eliminated. By ex vivo assay, FMN showed its antiparasitic effect for longer periods. Based on these results, FMN at 300 μg/mL concentration completely eliminated hydatid cyst protoscoleces after 60 minutes of exposure. While at a concentration of 150 μg/mL after 60 minutes, 89.6% of protoscoleces were destroyed. Formononetin noticeably increased (P < 0.001) the activity of caspase-3 and the permeability of protoscoleces dose-dependently.

Formononetin as a natural product showed promising effects on the protoscoleces of hydatid cysts, indicating that it can be considered a valuable scolicidal agent. However, additional investigations are necessary to evaluate its efficacy in animal models and human subjects.

Today, various drugs have been investigated as the primary or complementary treatment for coronavirus disease 2019 (COVID-19). N-acetylcysteine (NAC) has been used as a mucolytic in pulmonary diseases. This drug apparently contributes to the retrieval of the intracellular antioxidant system.

This study aimed to determine the efficacy of NAC in severe COVID-19 patients admitted to the intensive care unit (ICU).

This single-blinded randomized controlled phase III clinical trial included 40 patients with confirmed COVID-19 (based on polymerase chain reaction) admitted to the Shahid Mohammadi Hospital’s ICU, Bandar Abbas, Iran, in 2020. All cases had severe COVID-19. They were allocated randomly to two equal groups. Patients in the control group received standard drug therapy based on the treatment protocol of the national COVID-19 committee, while those in the NAC group received a single dose of intravenous NAC (300 mg/kg) upon admission to the ICU in addition to standard drug treatment. Clinical status and laboratory tests were done on admission to the ICU and then 14 days later or at discharge without knowing the patient grouping.

The two groups were comparable regarding age, gender, and other baseline laboratory and clinical parameters. At the final evaluation, respiratory rate (21.25 ± 4.67 vs. 27.37 ± 6.99 /min) and D-dimer (186.37 ± 410.23 vs. 1339.04 ± 2183.87 ng/mL) were significantly lower in the NAC group (P = 0.004 and P = 0.030, respectively). Also, a lower percentage of patients in the NAC group had lactate dehydrogenase (LDH) ≤ 245 U/L (0% vs. 25%, P = 0.047). Although the length of ward and ICU stay was shorter in the NAC group than in controls, the difference was statistically insignificant (P = 0.598 and P = 0.629, respectively). Mortality, on the other hand, was 75% in the control group and 50% in the NAC group, with no statistically significant difference (P = 0.102). Concerning the change in the study parameters, only the decrease in diastolic blood pressure (DBP) was significantly higher with NAC (P = 0.042). The intubation and mechanical ventilation rates were higher, while oxygen with mask and nasal oxygen rates were lower with NAC, but the difference was statistically insignificant.

Based on the current research, NAC is related to a significant decrease in RR, D-dimer, and DBP in severe COVID-19. Also, LDH was significantly lower in the NAC group than in the controls. More research with larger sample sizes is needed to validate the current study results.

Neuroblastoma (NB), a malignant sympathetic nervous system cancer, is the second most common type of pediatric tumor. Increasing the number of NB death emerges to design a new strategy for NB treatment. Nowadays, the development of natural compounds has gradually increased due to their ability to apoptosis induction. Tea catechin, a flavonoid compound, is one of the natural combinations which inhibit tumor growth and enhance tumor cell apoptosis. In the current study, the effects of pure catechin, doxorubicin (DOX), and their combination on a cellular model of NB [BE(2)C cells] are perused. (NB) a malignant sympathetic nervous system cancer is the second most common type of pediatric tumor. Increasing the number of NB death emerges to design a new strategy for NB treatment. Nowadays, the development of natural compounds has gradually increased due to their ability to apoptosis induction. Tea catechin, a flavonoid compound, is one of the natural combinations which inhibit tumor growth and enhance tumor cell apoptosis.

In the current study, the effects of pure catechin, doxorubicin (DOX), and their combination on a cellular model of NB [BE(2)C cells] are perused.

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was done to assess a response dose for each drug. Fluorescent Microscopic and cell cycle analyses were performed for apoptosis detection. Finally, Colony formation was performed to examine cell migration and invasion.

The MTT assay showed that catechin and DOX treatment inhibited the viability of the cells while the combination of their ineffective doses had more cytotoxic effects. However, these treatments could not inhibit the cell growth of the normal human fibroblast. Moreover, this combination reduced cell attachment, chromatin fragmentation, and G/S arrest in the cell cycle. The clonogenic assay demonstrated that colony size and numbers obviously reduced after ten days; therefore, Catchin and its combination with DOX suppressed cell capacities of clone formation and migration.

These results suggest that catechin, DOX, and their combination may inhibit the proliferation, invasion, and migration of BE(2)C Neuroblastoma cells in vitro while inducing cell apoptosis by arresting the cell cycle.

Burns are one of the most common injuries; however, there are few medications to repair burned skin. Although antibacterial drugs such as topical silver sulfadiazine may prevent wound infections, they usually cannot accelerate skin healing. Marshmallow (Althaea officinalis L.) has long been used in Iranian traditional medicine to deal with skin burns.

The present study aimed to evaluate the effect of hydroalcoholic and aqueous extract of A. officinalis on the histopathologic parameters of second-degree burns in mice.

The mice were randomly divided into nine groups (n = 6), including control and treatment groups. Experimental second-degree burns were induced on the dorsal skin of the mice by a metal plate (2 cm in diameter) under general anesthesia. Control and treatment groups were treated twice a day for 21 days topically. Normal saline was used for the control group, and hydroalcoholic and aqueous extracts of A. officinalis in three concentrations (1%, 2%, and 4%) were used for the treatment groups. All preparations were made in a hydrogel base. Finally, the histopathological parameters of the burned skin, including polymorphonuclear (PMN) migration, epithelialization, angiogenesis, and collagenization, were scored, and the total score of wound healing was calculated.

The findings showed that topical application of hydroalcoholic or aqueous extracts of A. officinalis accelerated the wound healing process. They reduced PMN migration, collagenization, epithelialization, and angiogenesis scores compared to the control group. There was a significant difference between the 4% hydroalcoholic extract group and the normal saline group.

Althaea officinalis may have been used as an adjunct medication to accelerate wound healing in skin burns.

Dicrocoeliasis and fascioliasis are foodborne parasitic diseases of the biliary tract, resulting from Dicrocoelium dendriticum and Fasciola hepatica causing extensive financial losses and serious health problems in ruminants. Due to low-performance medications, drug delivery is a tremendous project to improve interventions available for these diseases.

This study aimed to determine the anthelmintic properties of Ferula assa-foetida extract against F. hepatica and D. dendriticum using in vitro assay.

The effects of diverse concentrations of F. assa-foetida extract (400 - 1000 µg/mL) for 12-24 hours were examined for the treatment of D. dendriticum and F. hepatica. The anthelmintic efficacies were evaluated using scanning electron microscopy (SEM). The MTT assay was carried out to evaluate the cell viability of all cells in culture media.

The SEM images of treated worms by F. assa-foetida extract (200 µg/mL) confirmed excessive damage, which included an entire lack of sensory papillae and destruction of distinguished network structures and tegument vesicles. Variables of duration and concentration presented a considerable effect on both the mortality rate and the anthelmintic properties of F. assa-foetida; accordingly, as the time and concentration increased, the mortality rate became higher. Based on the MTT assay, the toxicity of F. assa-foetida at 800 µg/mL concentration was 8.7%. Therefore, it can be argued that F. assa-foetida had anthelmintic properties.

This is the first study that evaluated the impact of F. assa-foetida on liver flukes of D. dendriticum and F. hepatica. Therefore, it paved the way for further studies on the control of those trematodes. It is recommended to document and look into the indigenous understanding of viable medicinal plants to provide evidence for their use.