1. Introduction
Thuja trees are members of the order Pineales and the Cupressaceae family[1]. Thuja (T.) occidentalis, tree species that is native to eastern North America and is now planted as an ornamental tree in a variety of locations, including India, Brazil, Europe, among others[2]. Arbor vitae and white cedar are two more names for the same plant that are often used[3]. In the sixteenth century, native Indians in Canada recognized this plant as a medicine for the first time and also found it effective in the treatment of scurvy-induced weakness[4].
2. Medicinal potential of T. occidentalis
Evidence-based naturopathy for acute and chronic upper respiratory tract infections includes the use of T. occidentalis in combination with other immunomodulating herbs[5]. In traditional medicine, T. occidentalis has been used to treat a variety of conditions, including cystitis, rheumatism, amenorrhea, filiform warts, psoriasis, liver disease, bronchitis, uterine cancer, and diarrhoea among others[6,7,8]. It has also been used as hair growth enhancing agent[9]. The plant has also been reported to be anti-inflammatory in some recent studies[10,11]. Some scientists have also reported the insecticidal and vermicidal potential of T. occidentalis[12,13,14]. Essential leaf oil prepared from Thuja has been used to treat a variety of conditions, including cancer and intestinal worms and fungal infections[15,16]. T. occidentalis has also been found to be effective against Saccharomyces cerevisiae, Macrophomina, Fusarium solani, Aspergillus niger, Aspergillus flavus, Aspergillus parasitious and, Trichophyton rubrum, among others[17,18,19]. The secondary metabolites of plant have also shown substantial antimicrobial properties[20,21,22,23,24]. It also contains antiviral chemicals that have a high in vitro therapeutic activity against herpes simplex virus, many of whose results are either old or published in German[25]. The antiviral action of T. occidentalis has also been reported against Verruca vulgaris, HIV-1 and influenza A virus[26,27,28]. T. occidentalis has also been found to a potential source of antioxidants[28,29,30]. The ethanolic fraction of Thuja are antidiabetic and is found effective in the treatment of diabetic nephropathy[31,32]. The plant has also shown anti-atherosclerotic activity in a previous study[33]. The essential oil from the plant has also shown therapeutic potential against Polycystic Ovary Syndrome. It was found to exhibit an emmenagogue action against blocked menses, and is effective in the treatment of gynaecological illnesses because it alleviates the stomach discomfort, cramps, nausea, and exhaustion that are associated with menstrual cycles. By supporting hormonal balance via the release of specific hormones, such as estrogen and progesterone, it also aids in the regulation of the menstrual cycle and the maintenance of the health of the female reproductive organs[34]. It also stimulates blood circulation and the release of hormones, enzymes, gastric juices, acids, and bile, it is also known to promote peristaltic action, as well as stimulation of nerves, heart, and brain, among other features[35]. T. occidentalis in combination with other herbs is immunomodulatory[36,37,38]. The medicinal properties of T. occidentalis are presented in Table 1. Due to widespread overuse of antibiotics, microorganisms have developed an unprecedented level of resistance to antibiotics. This marks the beginning of the “postantibiotic period”, during which some bacterial infections may no longer be treated, as they were in the past[39]. T. occidentalis may provide a ray of hope in such a scenario.
;)
Table 1: Medicinal properties of Thuja occidentalis.
3. Biosynthesis of Thujone and its properties
Terpenoids, steroids, flavonoids, and polysaccharides are the compounds that have been found in T. occidentalis according to previous phytochemical reports[40]. The major constituents of the plant are shown in the Figure 1. Thujone is reported to be the bioactive principle behind T. occidentalis. It is a monoterpene with two epimeric forms: (−)-α-thujone and (+)-β-thujone[41]. Thujone’s IUPAC name is (4-methyl-1-(propane-2-yl) bicyclo [3.1.0] hexan-3-one (1S, 4R, 5R). The initial stage in the biosynthesis of thujone, as with other monoterpenes, is the formation of geranyl diphosphate also known as geranyl pyrophosphate (GPP) from dimethylallyl pyrophosphate and isopentenyl diphosphate, which is mediated by the enzyme geranyl diphosphate synthase. The first monoterpene, sabinene, is synthesized from GPP by the enzyme sabinene-synthase. The following step in the metabolic process involves changing sabinene into either trans (T. plicata) or cis-sabinol (Salvia officinalis). Thujones are synthesized via a NADPH-dependent stereoselective reduction of sabinone[42]. The pathway for biosynthesis of thujone is summarized in Figure 2.
Figure 1: Compounds present in Thuja occidentalis.
Figure 2: Biosynthesis of thujone from geranyl diphosphate also known as geranyl pyrophosphate (GPP). The first monoterpene, sabinene, is synthesized from GPP by the enzyme sabinene-synthase (SS). The following step in the metabolic process involves changing sabinene into either trans or cis-sabinol. Thujones are synthesized via a NADPH-dependent stereoselective reduction of sabinone[42].
In addition to T. occidentalis, thujone may be found in a wide range of plant species, such as Artemisia artemisia, Salvia officinalis, Salvia sclarea, Tanacetum vulgare, among others[43]. Its antimicrobial effect is thought to be due to the high concentration of α- and β-thujone[44,45]. It has been shown that thujone is highly effective as a mosquito repellent, antifeedant, and pesticide against both mammalian and insect herbivores[46,47,48]. Plants high in thujone have a long history of usage in traditional medicine for the treatment of a wide range of conditions, including bronchial catarrh, enuresis, cystitis, psoriasis, uterine carcinomas, amenorrhea, and rheumatism[48]. Thujone is also recommended for various types of cancers like skin tumorogenicity, ovarian cancers, adenocarcinomas, and glioblastomas[42,49,50]. The anticancerous effect of thujone is because of ER stress leading to the ectopic ER expression of ATF6 phosphorylation. This increases proapoptotic unfolded protein response targets including CHOP, which leads to cell death. The unfolded protein response pathway between the endoplasmic reticulum (ER) and mitochondria causes intrinsic apoptosis. This pathway involves anti-and pro-apoptotic molecules like Mcl-1 and Bcl-2. ER stress, proteasome-linked protein degradation, and mitochondrial dysfunction induce apoptosis through these pathways, making them interesting targets for anticancer treatments[50]. (Figure 3) summarizes the anticancerous mechanism of action of thujone.
Figure 3: Mechanism of action of thujone in cancer cells. The anticancerous effect of thujone is because of endoplasmic reticulum stress leading to the ectopic endoplasmic reticulum expression of ATF6 phosphorylation. This increases proapoptotic unfolded protein response targets including CHOP, which leads to cell death. The unfolded protein response pathway between the endoplasmic reticulum and mitochondria causes intrinsic apoptosis. This pathway involves anti- and pro-apoptotic molecules like Mcl-1 and Bcl-2. ER stress, proteasome-linked protein degradation, and mitochondrial dysfunction induce apoptosis through these pathways, making them interesting targets for anticancer treatments[50].
4. Therapeutic potential of T. occidentalis
The plant has been researched by various coworkers for its therapeutic potential. The different therapeutic properties of the plant are summarized in Figure 4. The following subsections discuss the therapeutic properties of T. occidentalis in detail.
Figure 4: Different medicinal properties of Thuja occidentalis.
4.1. Antibacterial properties
T. occidentalis extracts and isolated substances have shown antibacterial activities against a substantial number of bacterial species, as outlined in the Table 2. Previously, Bakht and colleagues evaluated and validated T. occidentalis antibacterial effectiveness against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and Gram-negative bacteria (Xanthomonas sp., Escherichia coli and Klebsiella pneumoniae). T. occidentalis extract was shown to be particularly effective against Klebsiella pneumoniae, a Gramnegative bacterium[20]. The Seo et al., 2017 study likewise validated these findings. Both Staphylococcus aureus and Escherichia coli were susceptible to the antibacterial effects of the essential oil that was isolated from T. occidentalis[21], Elansary and his colleagues made the discovery that the antibacterial activity of essential oil produced from T. occidentalis has a higher zone of inhibition than pharmaceuticals such as streptomycin and ampicillin[51]. It has also been shown that the essential oil of T. occidentalis was found to be efficient against the two bacteria that cause the greatest damage to plants, Agrobacterium tumefaciens and Erwinia carotovora var. carotovora, respectively[70]. It has been revealed that the hot water extracts of this plant had antibacterial activity against S. aureus and Escherichia coli[68] and the study conducted by Sah and co-workers agreed the findings against the same test bacteria[52]. Eltayeb and Hamid discovered that extracts of the plant are more efficient against Gram-positive bacteria than Gram-negative bacteria, and that active components in the extracts are more potent against skin-infected isolated bacteria. Also, the polarity of the solvent has a role in determining the level of antimicrobial activity[73]. The high concentration of α (alpha) and β (beta)-thujone in the plant is thought to be responsible for the plant’s antibacterial characteristics, since these compounds have also shown considerable antibacterial activity against microorganisms and are often employed in essential oils that possess antimicrobial properties[22].
Table 2: Antibacterial activity of Thuja occidentalis against different bacterial species.
4.2. Anti-fungal properties
The antimycotic qualities of T. occidentalis have been mentioned in Table 3.
Table 3: Antifungal activity of Thuja occidentalis against different fungal species.
In addition to posing health risks to people and animals, fungi may also reduce crop production in the agricultural sector by harming plants. Many researchers are racing to identify various plants with the potential to serve as antimycotic medications, since these treatments are necessary for the treatment of fungal diseases. In early 2000s, Gupta and Srivastava evaluated the antifungal activity against Aspergillus flavus and Aspergillus niger and confirmed the efficacy of T. occidentalis[17]. Considering that Aspergillus flavus is responsible for cutaneous aspergillosis and that Aspergillus niger is responsible for otomycosis, it is evident two fungi pose a significant threat to human health. The conclusions of the research study that was carried out by Bellili and his fellow researchers were validated by the essential oil that was derived from the leaves and cones of T. occidentalis. This essential oil showed antibacterial action against yeast (Candida albicans) and two types of fungi (Aspergillus flavus and Aspergillus niger), further they also determined the antibacterial activity against different Gram-positive and Gramnegative bacteria[56]. T. occidentalis has been found effective against different fungal strains like Yersinia aldovae, Aspergillus parasiticus, Saccharomyces cereviciae, Trichophyton rubrum, and Candida albicans[57]. The study conducted by Chinche et al., 2018 confirmed the promising results of T. occidentalis against Ashbya gossypii to treat stigmatomycosis diseases in cotton plants[18].
4.3. Anti-oxidant properties
In terms of the free radicals produced by cell metabolism, phenolic substances are best characterized by their antioxidant activity[72]. In the 2014 research done by Kumar and colleagues, the radical-scavenging activity of Thuja extracts was compared to that of peach extracts. The research found that Thuja extracts had more reducing power than peach extracts, that is, (3.32±0.01) and (0.49±0.01), at OD700, respectively[29]. The same findings were validated by Nazir and colleagues, who found that the methanolic extract of T. occidentalis had a stronger antioxidant capacity than other plant extracts[30]. In another study, Ahmad, and colleagues, determined the DPPH scavenging activity of T. occidentalis at different concentrations that were found to be different, at 1 mg/mL, 5 mg/mL, 10 mg/mL, 50 mg/mL, 100 mg/mL they showed significant reductions 92.45%, 73.41%, 46.99%, 62.43%, and 61.57%, respectively[12]. Stan and co-workers confirmed the antioxidant potential of the Thuja extracts using different techniques to measure the mother tincture's antioxidant capacity; 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (DPPH), oxygen radical absorbance capacity assay, and nitric oxide radical scavenging assay (NO). The DPPH scavenging activity of T. occidentalis was 88.1%, oxygen radical absorbance capacity assay was 50.0%, and NO was 78%, respectively[78]. DPPH activity was also measured and compared to the reference medication by Dubey and Batra in 2009. At a concentration of 300 µg/mL, Thuja extracts showed (73.346%±1.040%) DPPH scavenging activity with 202.457 µg/mL IC50 value[8].
4.4. Anti-viral properties
According to the findings of Beuscher and Kopanski, T. occidentalis contains compounds that show antiviral action against the herpes simplex virus. This suggests that it may have therapeutic efficacy against this virus when tested in vitro[25], It has been shown that the polysaccharides that are derived from T. occidentalis have an antiviral impact as well as an immune boosting effect, having the potential to suppress HIV-1 and influenza A[79]. An aqueous-ethanolic extract of T. occidentalis herbal, in combination with other extracts; Baptisiae tinctoriae radix, Echinacea purpureae radix, and Echinacea pallidae radix was tested on mice. The results showed, the extract significantly enhances the titer of specific antibodies in the serum of treated animals (sheep) and causes an increase in the number of splenic plaque-forming cells (PFC)[36]. The findings of Gohla and co-workers showed that at a final concentration of 625 g/mL, Thuja polysaccharides (TPS), which are derived from the T. occidentalis tree, suppress the human immunodeficiency virus-dependent cell death which causes acquired immune deficiency syndrome[26]. An infection with Verruca vulgaris induced by the human papillomavirus increases the likelihood of developing squamous cell cancer. The many therapeutic techniques that are available only provide a limited response. A case of a recipient of a renal allograft with several warts that did not respond to cryotherapy or radiosurgery. Eventually, one of the warts turned malignant and necessitated the amputation of a finger. The resistant warts on the other fingers were healed using an extract from the T. occidentalis. The extract only caused superficial scarring to appear[27]. T. occidentalis has several useful immunological qualities that may also be used to the treatment of respiratory viral infections[80].
4.5. Anti-cancerous properties
T. occidentalis has been used for a very long time by practitioners of traditional medicine as a mother tincture for the treatment of a broad number of ailments, including moles and tumors, in addition to a wide variety of skin and other illnesses. The anti-proliferative and apoptosis-inducing capabilities of the Thuja plant and the thujone-rich fraction isolated from it were investigated by Biswas and colleagues for their potential anti-cancer effects in a malignant melanoma cell line. The results indicate that both the Thuja plant and the thujone-rich fraction has anticancer potential. In addition, when comparing their anticancer potential, the thujone-rich fraction of T. occidentalis showed much more cytotoxic, anti-proliferative, and apoptotic activities on A375 cells in vitro[15].
According to research that was conducted in 2010 by Frenkel and colleagues, it seems that homoeopathic medications, when taken in extremely low dosages, have selective cytotoxic effects on the human breast cancer cell lines MCF-7 and MDA-MB-231. Alterations in the expression of cell cycle regulatory proteins have been shown to be associated to both the delay and stoppage of the cell cycle as well as the promotion of cell death via the activation of the apoptotic cascade[81]. T. occidentalis, as discovered by Sunila and coworkers in the year 2011, may inhibit the production of excessive amounts of inflammatory cytokines[82].
In the report from the year 2020, Jean-Lionel states that mice administered T. occidentalis lived longer than placebo-treated mice and that an alcoholic extract of the plant was helpful in blocking the spread of melanoma cells to the lungs[83]. The extract of T. occidentalis demonstrated exceptional apoptotic capacity against lung cancer cells and the ability to ameliorate BaP-induced lung damage[84].
The recently published research by Loonat and colleagues in 2022 demonstrates that A549 cells were treated with T. occidentalis and with combination therapy using photodynamic treatment before being subjected to 660 nm laser irradiation. An examination of cellular morphology was performed using inverted light microscopy and Hoechst staining. The cells were subjected to biochemical testing, including the lactate dehydrogenase assay, the adenosine triphosphate assay, and the trypan blue exclusion test. Antitumor responses of T. occidentalis were amplified with photoactivation in photodynamic therapy. These effects made it possible to provide advantages beyond those of tincture treatment alone[85].
There are several different cancer cell lines that have been tested with the extract derived from Thuja leaves, and the results have been encouraging[16,86]. Singh and coworkers showed the cytotoxic effect of T. occidentalis on cervical cancer cells in vitro. Similar effect was observed by Pal et al. by using T. occidentalis homeopathic mother tincture[87,88].
4.6. Immunomodulatory activities
T. occidentalis has been reported to increase WBC count in the treated swiss mice infected with bacteria. This confirms the immunomodulatory potential of the plant[55]. Bodinet and Freudenstein examined the immunological responses of mice to an aqueous-ethanolic extract of the T. occidentalis herb and other plant extracts. The number of antibody-producing cells in the spleen and the hemagglutination titers both rose after receiving a dosage of 4 mg/kg of body weight[36]. In addition, the author observed an increase in the proliferation rates of spleen cells isolated from both NMRI and C3H/He J mice[37]. The polysaccharide fractions that were extracted from the T. occidentalis were shown to activate CD4+ T cells[38]. Spleen cells that were extracted from mice that had been treated with T. occidentalis generated increased levels of immunostimulatory cytokines ex vivo. These cytokines were IL-2 and IFN-γ. Immune response to tumor-bearing mice might be improved by T. occidentalis and TPS activation of NK cells and antibody-dependent cellular immunological responses. Perhaps, it might reduce the increased amount of pro-inflammatory cytokines in B16F-10 melanoma cells. Increased IL-2 levels can boost natural immunity by activating NK cells. In addition, the therapy with these drugs boosted the amount of the endogenous tumor inhibitor TIMP. These findings demonstrated the immune-stimulating action of T. occidentalis and TPS in rats with metastatic tumors. It has been demonstrated that the T. occidentalis polysaccharide fraction, also known as TPS, is an inducer of the CD4+ fraction of the human peripheral blood T-cell subset[89]. Researchers have discovered that the CD4+ fraction of the T-cell subset in human peripheral blood may be stimulated by a compound found in Thuja called thuja polysaccharide fraction (TPSg). FACS analysis also characterized the TPS g fraction stimulated CD4+ T-cell fraction. TPSg increases the production of IL-1 beta, IL-2, IL-3, IL-6, gamma-IFN, G-CSF, GM-CSF, and TNF-beta in monocyte/macrophage cells and PBL cultures. The capacity of TPS to stimulate cell proliferation and clustering leads in an increase in CD4+ T-helper/inducer cells and the subsequent production of interleukin-2 (IL-2). T-helper cells proliferate and develop into fully functional cells via the processes of proliferation and differentiation[90].
4.7. Preventive effect on gastric ulcer
The observations of an alcohol-induced stomach ulceration model indicate that treatment with an extract of the aerial portion of T. occidentalis resulted in a substantial reduction in the ulcer index. In alcohol-induced stomach ulcers, a reduction in mucosal resistance is the most relevant etiology factor when compared with a positive control. However, there is evidence to suggest that alcohol stimulates the production of protein into gastric juice. The amount of glutathione in the stomach mucosa is decreased when an ulcer is induced by ethanol usage[91]. T. occidentalis ethanol extract has been shown to significantly prevent stomach ulcers in rats caused by both ethanol and aspirin, according to research published in 2009 by Deb et al. The amount of stomach acid was observed to be reduced by 45% (P<0.05) and 69% (P<0.001) in the two doses of 200 and 400 mg/kg of T. occidentalis methanolic extract, respectively, in previous research. Gastric epithelial regeneration was most evident in rats given 400 mg/kg. T. occidentalis has been shown to have antioxidant properties, and this research confirms that these properties contribute to the fruit's antiulcer effect[92].
4.8. Protection against arthritis
To determine whether T. occidentalis possesses anti-arthritic capabilities, Patil and coworkers conducted an experiment on Wistar rats. As part of their research, they compared the effects of pure T. occidentalis to those of various dilutions of the homoeopathic treatment. Based on their findings, the researchers concluded that T. occidentalis is effective against arthritis. In addition, they concluded that a 6cH homoeopathic dilution of the medicinal plant was more efficacious than the undiluted version of the same plant[6]. Dr. Jenifer Antoni observed the same findings and reported them when she was treating a patient who appeared with a range of symptoms, including discomfort in the knees and numbness in the neck region. The patient was prescribed rhus tox 1M and Thuja as a remedy, which led to a gradual improvement in the patient’s symptoms as well general state of health[7].
4.9. Protection against skin warts
A recently published case study revealed that T. occidentalis could be a useful therapy for many filiform warts. Within 41 weeks of treatment, a patient with numerous facial warts of diverse diameters (ranging from 1 mm to 10 mm) was successfully treated with T. occidentalis in a variety of different potencies and the patient's condition improved significantly[93]. In fact, the Thuja homeopathic ointments and oils are readily available in market for the treatment of skin warts.
4.10. Therapeutic potential against polycystic ovary syndrome
Küpeli-Akkol and coworkers investigated the potential benefits of T. occidentalis and its constituents for the treatment of polycystic ovary syndrome. Results indicated that estradiol and progesterone levels increased substantially, whereas luteinizing hormone and testosterone levels decreased significantly. T. occidentalis and its component thujone groups also had significantly reduced plasma concentrations of low-density lipoprotein-cholesterol, leptin, and glucose compared to the values seen in the control group[34].
4.11. Hepatoprotective activity
Earlier research revealed that the ethanolic fraction of T. occidentalis might have a hepatoprotective benefit against CCL4-induced liver damage in rats. According to the findings of the research conducted, the ethanolic fraction had a beneficial impact. In a model of CCL4-induced liver damage that was either acute or chronic, a single injection of T. occidentalis at a dosage of 400 mg/kg, demonstrated significant protective benefits against liver damage. This effect was seen in both models. Following the completion of the treatment, a histological examination was carried out in order to assess the level of hepatoprotection that had been attained[94]. In another study, increased levels of SGPT and alkaline phosphatase in the liver and serum in gamma irradiated mice were lowered by T. occidentalis ethanol extract[95].
4.12. Anti-hyperglycemic activity
An ethanolic fraction of T. occidentalis (EFTO) was administered to wistar albino rats in research by Dubey and Batra in 2008 to investigate its possible anti-diabetic effects. The prevalence of diabetes in alloxan-induced cases was studied by measuring fasting blood sugar, blood glutathione levels, and serum biochemical analyses. A dosage of 200 mg/kg of the extract was demonstrated to have a significant impact on diabetes. Due to EFTO’s anti-oxidant effect, glutathione levels also rose significantly[31]. According to Tyagi et al., T. occidentalis has the potential to ameliorate renal and liver function and enhance glucose homeostasis in alloxan-induced diabetes. Therefore, the novel oral antidiabetic medication may originate in the branches of the T. occidentalis tree[96].
4.13. Anti-atherosclerotic property
An investigation of the lipid peroxidation activity and associated hypolipidemic activity of an ethanolic extract of T. occidentalis was carried out on rats by Dubey and colleagues. The extract's hypolipidemic effect significantly decreased blood levels of cholesterol, LDL, and triglycerides when administered at doses of 200 mg and 400 mg/kg of body weight, respectively. Strong evidence suggests that T. occidentalis has an anti-atherosclerotic effect, as shown by an improvement in the ratio of HDL to total cholesterol and a decrease in the atherogenic index in groups that were given EFTO[33,97].
4.14. Neuroprotective efficacy
In recent study, Bhargava and coworkers induced diabetic neuropathy in male Wistar rats using streptozotocin and nicotinamide to test the neuroprotective effects of T. occidentalis using a single dose of streptozotocin (65 mg/kg). Different doses of gabapentin and T. occidentalis hydroalcoholic extracts were administered to Wistar rats for a month. Specifically, the results demonstrated that T. occidentalis is an effective treatment for diabetic neuropathy because it increases neuronal activity while reducing hyperglycemic-induced oxidative stress and inflammatory indicators[32].
4.15. Insecticidal activity
Insects have become resistant to synthetic pesticides, which has led to an increase in environmental concerns, which in turn has led to a rise in interest in the use of medicinal herbs as insecticides during the last decade[98]. An investigation of the effectiveness of T. occidentalis as an insecticide, carried out by Ahmad and his fellow researchers on T. castaneum. Permethrin was employed as a reference standard for determining the insecticidal action, and at 100 mg/2 mL, the percentage mortality was determined to be 100%. The mortality rates of 20%, 20%, and 40% were recorded, respectively, after being exposed to 10 mg/2 mL, 50 mg/2 mL, and 100 mg/2 mL of T. occidentalis[12]. The essential oil of T. occidentalis has been reported to have comparable biological effects on stored grain insects similar to the tropical oils such as Ocimum oils[99].
4.16. Anthelmintic activity
The anthelmintic activity of T. occidentalis was evaluated by Dasari and co-workers in 2021, using the adult Indian earthworm species Pheretima posthuma, which has morphological and physiological characteristics with intestinal roundworms. The dosages tested were 10, 20, and 50 mg/mL. The highest dosage tested, which was 50 mg/mL, showed a significant anthelmintic action when compared to the standard reference, which was piperazine citrate at 10, 20, and 50 mg/mL. In treating helminthic infestations, it was shown that herbal remedies and synthetic pharmaceuticals were equally beneficial. However, the methanolic extract of T. occidentalis showed the greatest promise and had the highest anthelmintic activity[14]. Boyko and Brygadyrenko reported the anthelminthic activity of aqueous solution of T. occidentalis against Strongyloides papillosus[100].
4.17. Antipyretic activity
T. occidentalis methanol extract was shown to be effective as an antipyretic in rabbits. When administered at 100 and 200 mg/kg of body weight, it has the same antipyretic and temperature-regulating effects as paracetamol[101]. T. occidentalis, Linn was tested for antipyretic efficacy against TAB (Typhoid) vaccination and PGE1-induced rabbit pyrexia. In TAB vaccine-induced fever, oral 100 and 200 mg/kg doses decreased fever and stabilized body temperature, equivalent to the reference medication (Paracetamol). Unlike the conventional medicine, PGE1 decreased pyrexia (Aspirin).
4.18. Radioprotective activity
Researchers found that T. occidentalis provides protection against radiation by increasing TNF-α, IL-6, and IL-1 activities[1]. Sunila and Kuttan found that T. occidentalis reduced gamma-induced toxicity in Swiss albino mice. Therefore, alkaline phosphatase, pyruvate transferase, and lipid peroxidation were all lowered by the T. occidentalis alcoholic extract[96].
4.19. Antileishmanial efficacy
Not much work has been done on the antiprotozoal potential of T. occidentalis. However, in a study, Rani and Dantu reported moderate antileishmanial efficacy of T. occidentalis[102].
4.20. Treatment of tongue lesions
A recent study done by Dr. Bed Prakash Gond reported the effectiveness of T. occidentalis in the treatment of Mucocele or the nodular lesions of the tongue. The treatment was given to a 4 year female child whose Mucocele of the tongue was resolved within a month after treatment with low potency (30CH) of T. occidentalis[103].
5. Conclusions
Many medicinal plants have had their healing powers recognized, recorded, and passed down through history since the emergence of humans and advanced civilizations. Until now, successive civilizations have continuously enhanced pre-existing infrastructure and developed new sources of wealth. It is because of this commitment that we now have a highly refined method for caring for and using therapeutic plants. T. occidentalis could be possible the future super-plant as it is widely used in both traditional homoeopathy and modern, evidence-based phytotherapy. In vitro and in vivo models have shown its immunopharmacological potential, including its immunostimulatory, anti-cancer, anti-bacterial, anti-fungal, and antiviral activities. Despite these encouraging results, more definitive evidence from clinical studies is needed, notably with only the herbal compound.
6. Limitations
T. occidentalis is a plant with wide medicinal potential but it has certain limitations. Thujone, the bioactive principle behind the plant has certain side effects. It is hallucinogenic and may cause epileptic seizures. It can cause stomach aches and can lead to renal failure also[104,105,106,107,108,109]. However, these effects may be ameliorated by nano-encapsulation, charcoal treatment, or UV irradiation.
7. Future perspectives
There are approximately 500000 different plant species all over the world, the vast majority of which have not yet been investigated in the context of medical practices. As a result of this, there is reason to be optimistic regarding the potential of therapeutic herbs. Research in medicine that is now being done as well as research that has not yet been done can be helpful in the diagnosis, treatment, and prevention of illnesses. In healthcare systems all around the world, T. occidentalis is used as a source of adjuvant treatment, which is used not only to treat diseases but also to prevent diseases and to keep people healthy. Despite the rich history of traditional medicinal use of T. occidentalis, modern scientific investigation and identification of active plant components and their effects indicate the potential for the development of novel therapeutic applications and the creation of nature-based products. In order to accomplish this goal, it is essential to conduct extensive research in order to control the quality and the formulation in order to justify their use in the modern medical system; subsequently, studies on animals and clinical trials are required in order to make use of the benefits offered by this plant. In addition, a workable strategy for the preservation of these resources ought to be created as part of the process of developing medicines derived from T. occidentalis.
Conflict of interest statement
The authors declare that there is no conflict of interest.
Funding
The authors received no extramural funding for the study.
Authors’ contributions
MT and TK wrote the manuscript. MT has created all the figures. TK and RCS has edited the manuscript. All the authors have contributed to the final version of the manuscript.
REFERENCES
1. Caruntu S, Ciceu A, Olah NK, Don I, Hermenean A, Cotoraci C. T. occidentalis L. (Cupressaceae): Ethnobotany, phytochemistry and biological activity Molecules. 2020;25(22):5416
2. Chang LC, Song LL, Park EJ, Luyengi L, Lee KJ, Farnsworth NR, et al Bioactive constituents of T. occidentalis J Nat Prod. 2000;63(9):1235–1238
3. Thummar I, Pramanick M, Singh S, Desai P. Formulation of mixed variety of lotion prepared by T. occidentalis-Q and Allium cepa-Q in definite proportion J Pharmacogn Phytochem. 2023;12(1):226–229
4. Millspaugh CF. American medicinal plants; an illustrated and descriptive guide to the American plants used as homopathic remedies: their history, preparation, chemistry, and physiological effects 1887 New York Boericke & Tafel
5. Reitz HD, Hergarten H. Immunmodulatoren mit pflanzlichen Wirkstoffen-2. Teil: eine wissenschaftliche Studie am Beispiel Esberitox
® N Notabene Medici. 1990;20:304–306
6. Patil S, Mahajan U, Goyal S, Belemkar S, Patil C. Homoeopathic drug dilutions of T. occidentalis attenuate complete Freund’s adjuvant-induced arthritis in Wistar rats Indian J Res Homoeopathy. 2018;12(4):202
7. Jenifer ADJ. Role of Thuja as an intercurrent remedy in Osteoarthritis[Accessed on 19 January 2023] [Online] Available from:
https://www.homeobook.com/role-of-thuja-as-an-intercurrent-remedy-in-osteoarthritis/.
8. Dubey SK, Batra A. Study of anti-oxidant and anti-inflammatory activity from ethanol fraction of T. occidentalis Linn Res J Sci Tech. 2009;1(1):39–42
9. Shimada K. Contribution to anatomy of the central nervous system of the Japanese upon the vermal arbour vitae Okajimas Folia Anat Jpn. 1956;28:207–227
10. El-Sayed, Abdel-Aziz AA. Ameliorative and anti-inflammatory properties of T. occidentalis in phenytoin-induced hepatic and renal dysfunctions in male albino rats Environment Asia. 2023;16(1):157–168
11. Bharti K, Sharma M, Vyas GK, Sharma S. A review on phytochemical pharmacological and biological activities of T. occidentalis AJPRD. 2022;10(2):111–115
12. Ahmad M, Saeed F, Mehjabeen, Jahan N. Evaluation of insecticidal and anti-oxidant activity of selected medicinal plants J Pharmacogn Phytochem. 2013;2(3):153–158
13. Song HJ, Yong SH, Kim HG, Kim DH, Park KB, Shin KC, et al Insecticidal activity against Myzus persicae of terpinyl acetate and bornyl acetate in
Thuja occidentalis essential oil Horticulturae. 2022;8(10):969
14. Dasari PK, Sai GJ, Kumari BNVL, Keerthana M, Satyanarayana T. Phytochemical screening and in-vitro anthelmintic activity of T. occidentalis leaves Int J Mod Pharm Res. 2021;5(3):208–212
15. Biswas R, Mandal SK, Dutta S, Bhattacharyya SS, Boujedaini N, Khuda-Bukhsh AR. Thujone-rich fraction of T. occidentalis demonstrates major anti-cancer potentials: Evidences from in vitro studies on A375 cells Evid Complem Altern Med. 2011;2011:1–16 doi:
https://doi.org/10.1093/ecam/neq042
16. Sunila ES, Kuttan G. A preliminary study on antimetastatic activity of T. occidentalis L. in mice model Immunopharmacol Immunotoxicol. 2006;28(2):269–280
17. Gupta G, Srivastava AK. In-vitro activity of T. occidentalis Linn. against human pathogenic Aspergilli Homoeopath Herit. 2002;27:5–12
18. Chinche AD, Kathade SA, Anand PK, Jadhav AB, Kunchiraman BN, Shinde CH. In-vitro study for anti-fungal activity of homoeopathic medicines against plant fungus Ashbya gossypii Int J Res Anal Rev. 2018;5(4):466–470
19. AL-Enawey AW, Saadedin SMK, Al-Khaldi SAM. Antifungal activity, GC-MS analysis of T. occidentalis essential oil with gene expression Iraq J Biotechnol. 2020;3(19):33–41
20. Bakht J, Zafar Z, Ahmad J, Khan S. Antibacterial activity of the crude extracts from medicinally important T. occidentalis Pak J Pharm Sci. 2020;33(2):627–630
21. Nelson S. The antibacterial activity of essential oils from Tagetes erecta and T. occidentalis Cantaurus. 2019;27:29–33
22. Tsiri D, Graikou K, Pobłocka-Olech L, Krauze-Baranowska M, Spyropoulos C, Chinou I. Chemosystematic value of the essential oil composition of Thuja species cultivated in Poland-antimicrobial activity Molecules. 2009;14(11):4707–4715
23. Tekaday D, Antony R, Jain S. Antimicrobial, antioxidant and phytochemical investigation of T. occidentalis (Arbor vitae) leave extract GSC Biol Pharm Sci. 2020;12(3):108–116
24. Chajduk M, Gołębiowski M. Seasonality study of extracts from leaves of T. occidentalis L Acta Biologica Cracoviensia Series Botanica. 2022;64(10):7–14
25. Beuscher N, Kopanski L. Purification and biological characterization of antiviral substances from T. occidentalis Planta Med. 1986;52(6):555–556
26. Gohla SH, Zeman RA, Gartner S, Jurkiewicz E, Schrum S, Haubeck HD, et al Inhibition of the replication of HIV-1 by TPSg, a polysaccharide-fraction isolated from the Cupressaceae ‘T. occidental L’ AIDS Res Hum Retroviruses. 1990;6:131.
27. Joseph R, Pulimood SA, Abraham P, John GT. Successful treatment of Verruca vulgaris with T. occidentalis in a renal allograft recipient Indian J Nephrol. 2013;23:362–364
28. Shaffique S, Anwer H, Asif HM, Akram M, Rehman A, Ahmed S, et al In vitro evaluation of antioxidant activity of homeopathic mother tincture and total phenolic content RADS J Pharm Pharm Sci. 2020;8(1):26–30
29. Kumar Y, Ali J. Antioxidant potential of Thuja (T. occidentalis) cones and peach (Prunus persia) seeds in raw chicken ground meat during refrigerated (4±1 °C) storage J Food Sci Technol. 2014;51:1547–1553
30. Nazir MZ, Chandel S, Sehgal A. In vitro screening of antioxidant potential of T. occidentalis J Chem Pharm Sci. 2016;8(8):283–286
31. Dubey SK, Batra A. Anti-diabetic activity of T. occidentalis Linn Res J Pharm Tech. 2008;1(4):362–365
32. Bhargava SK, Singh TG, Mannan A, Singh S, Singh M, Gupta S. Pharmacological evaluation of T. occidentalis for the attenuation of neuropathy via AGEs and TNF-α inhibition in diabetic neuropathic rats Environ Sci Pollut Res Int. 2022;29(40):60542–60557
33. Dubey SK, Batra A. Role of phenolics in anti-atherosclerotic property of T. occidentalis Linn Ethnobot Leafl. 2009;2009(6):791–800
34. Küpeli Akkol E, İlhan M, Ayşe Demirel M, Keleş H, Tümen I, Süntar İ. T. occidentalis L. and its active compound, α-thujone: Promising effects in the treatment of polycystic ovary syndrome without inducing osteoporosis J Ethnopharmacol. 2015;168:25–30
35. Cummings S, Ullman D. Everybody's guide to homeopathic medicines: Safe and effective remedies for you and your family. 3rd version 1997 New York Putnam
36. Bodinet C, Freudenstein J. Effects of an orally applied aqueous-ethanolic extract of a mixture of Thujae occidentalis herba, Baptisiae tinctoriae radix, Echinaceae purpureae radix and Echinaceae pallidae radix on antibody response against sheep red blood cells in mice Planta Med. 1999;65(8):695–699
37. Bodinet K. Immunopharmacological studies on an
herbal immunomodulator Inaugural Dissertation. 1999 Greifswald
38. Gohla SH, Haubeck HD, Schrum S, Soltau H, Neth RD. Activation of CD4-positive T cells by polysaccharide fractions isolated from the Cupressaceae T. occidentalis L. (Arborvitae) Haematol Blood Transfus. 1989;32:268–272
39. Hochvaldová L, Panáček D, Válková L, Prucek R, Kohlová V, Večeřová R, et al Restoration of antibacterial activity of inactive antibiotics via combined treatment with a cyanographene/Ag nanohybrid Sci Rep. 2022;12(1):5222
40. Naser B, Lund B, Henneicke-von Zepelin HH, Köhler G, Lehmacher W, Scaglione F. A randomized, double-blind, placebo-controlled, clinical dose-response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of patients with common cold Phytomedicine. 2005;12(10):715–722
41. Perry NB, Anderson RE, Brennan NJ, Douglas MH, Heaney AJ, McGimpsey JA, et al Essential oils from dalmatian sage (Salvia officinalis L.): Variations among individuals, plant parts, seasons, and sites J Agric Food Chem. 1999;47(5):2048–2054
42. Nemeth EZ, Nguyen HT. Thujone, a widely debated volatile compound: What do we know about it? Phytochem Rev. 2020;19:405–423
43. Tamer CE, Suna S, Özcan-Sinir G. Toxicological aspects of ingredients used in nonalcoholic beverages Non-alcoholic beverages. 2019 Cambridge Elsevier:441–481
44. Baser KHC, Demirci B, Demirci F, Kocak S, Akinci C, Malyer H, et al Composition and antimicrobial activity of the essential oil of Achillea multifida Planta Med. 2002;68:941–943
45. Sivropoulou A, Nikolaou C, Papanikolaou E, Kokkini S, Lanaras T, Arsenakis M. Antimicrobial, cytotoxic, and antiviral activities of Salvia fructicosa essential oil J Agric Food Chem. 1997;45:3197–3201
46. Maia MF, Moore SJ. Plant-based insect repellents: A review of their efficacy, development and testing Malar J. 2011;10(S1):S11
47. Rojht H, Meško A, Vidrih M, Trdan S. Insecticidal activity of four different substances against larvae and adults of sycamore lace bug (Corythucha ciliata [Say], Heteroptera, Tingidae) Acta Agriculturae Slovenica. 2009;93(1):31–36
48. Wróblewska-Kurdyk A, Gniłka R, Dancewicz K, Grudniewska A, Wawrzeńczyk C, Gabryś B. β-Thujone and its derivatives modify the probing behavior of the peach potato aphid Molecules. 2019;24(10):1847
49. Torres A, Vargas Y, Uribe D, Carrasco C, Torres C, Rocha R, et al Pro-apoptotic and anti-angiogenic properties of the α/β-thujone fraction from T. occidentalis on glioblastoma cells J Neurooncol. 2016;128(1):9–19
50. Lee J, Park H, Lim W, Song G.
Therapeutic potential of α, β-thujone through metabolic reprogramming and caspase-dependent apoptosis in ovarian cancer cells J Cell Physiol. 2021;236(2):1545–1558
51. Elansary HO, Abdelgaleil SAM, Mahmoud EA, Yessoufou K, Elhindi K, El-Hendawy S. Effective antioxidant, antimicrobial and anticancer activities of essential oils of horticultural aromatic crops in northern Egypt BMC Complement Altern Med. 2018;18(1):214
52. Sah SN, Regmi S, Tamang MK. Antibacterial effects of Thuja leaves extract Int J Appl Sci Biotechnol. 2017;5(2):256–260
53. Bellili S, Aouadhi C, Dhifi W, Ghazghazi H, Jlassi C, Sadaka C, et al The influence of organs on biochemical properties of Tunisian T. occidentalis essential oils Symmetry. 2018;10(11):649
54. Jahan N, Ahmad M, Mehjabeen Zia-ul-haq M, Alam SM, Qureshi M. Antimicrobial screening of some medicinal plants of Pakistan Pah J Bot. 2010;42:4281–4284
55. Verma SK, Singh SK, Singh S, Mathur A. Evaluation of immunomodulatory and microbicidal potential of T. occidentalis Environ Conserv J. 2010;11(3):85–88
56. Khan ZS, Khan AM, Bhosle N, Nasreen S. Antimicrobial activity of leaf extracts of T. occidentalis L Bioinfolet. 2009;6(2):142
57. Francis A, Yaw DB, Christian A, George HS, Vivian EB, Frank BO. Antibacterial resistance modulatory properties of selected medicinal plants from Ghana Afr J Pharm Pharmacol. 2019;13(5):57–69
58. Gupta S, Chourey A, Gupta D, Agrawal A, Gupta S. Bio-control of clinical bacterial isolates associated with urinary tract infection using wild medicinal plant extract J Nat Prod Plant Resour. 2015;5(3):23–30
59. Mandal A, Basak GK, Karmakar A, Chowdhury T, Chakraborty S, Biswas R, et al Isolation of octacosane-10-ol-21-ene from T. occidentalis L. cone and its antibacterial activity IJGHC. 2019;8(2):67–72
60. Chaudhary P, Gauni B, Mehta K. Carotenoid and antibacterial analysis of T. occidentalis Indian J Appl Res. 2015;5(7):112–114
61. Kanawaria SK, Sankhla A, Jatav PK, Yadav RS, Verma KS, Velraj P, et al Rapid biosynthesis and characterization of silver nanoparticles: An assessment of antibacterial and antimycotic activity Appl Phys A. 2018;124(4):320
62. Acosta Castellón M, García García D, Castro Méndez I, Rodríguez Jorge M, Crespo M. Obtençäo e controle de qualidade da tintura-mäe de Thuya occidentalis Pesqui homeopática. 2000;15(1):67–75
63. Dumitrescu E, Kraunovic MC, Orăşan-Alic AS, Moruzi RF, Mohamed AE, Doma AO, et al Study of volatile compounds and antimicrobial activity of Thuja essential oils Med Vet/Vet Drug. 2021;15(2):63–75
64. Dubey A, Raja W, Bairagi Y. Evaluation of antimicrobial activity of T. occidentalis extract against some human pathogenic bacteria WJPLS. 2017;3(10):97–103
65. Nidhi P, Kumari R, Thakur S, Devi R, Sharma R, Kashyap S, et al Role of essential oils of medicinal plants (Eucalyptus globulus, T. occidentalis, Rosmarinus officinalis, Lavandula officinalis) to treat broad spectrum bacterial and fungal pathogens and as antioxidants in food and health SSRN Electron J. 2018 doi:
http://dx.doi.org/10.2139/ssrn.3299291
66. Seo KS, Jin SW, Choi S, Yun KW. Antibacterial activity of T. occidentalis, Thuja orientalis and Chamaecyparis obtuse Int J Pharm Qual Assur. 2017;8(3):78–81
67. Nawaz H, Sumreen L, Asif HM, Qamar S, Tanveer R, Shaheen G, et al Screening of antibacterial potential of some selected homoeopathic mother tinctures against common uropathogens: Research paper RADS J Pharm Pharm Sci. 2022;10(2):55–60
68. Al-Roubai SMH, Al-Rawe MHA, Mahmood A, Khaleefah AA. Inhibition activity of T. occidentalis fruit extract against Staphylococcus aureus and E. coli isolated from cases of mastitis in Baghdad/Iraq Biochem Cell Arch. 2020;20(2):3579–3358
69. Lindberg LE, Willför SM, Holmbom BR. Antibacterial effects of knotwood extractives on paper mill bacteria Ind Microbiol Biotechnol. 2004;31(3):137–147
70. Ibáñez MD, López-Gresa MP, Lisón P, Rodrigo I, Bellés JM, González-Mas MC, et al Essential oils as natural antimicrobial and antioxidant products in the agrifood indus J Method Model Simul. 2020;12:55–69
71. Badawy MEI, Abdelgaleil SAM. Composition, and antimicrobial activity of essential oils isolated from Egyptian plants against plant pathogenic bacteria and fungi Ind Crop Prod. 2014;52:776–782
72. Leopolsdini M, Russo N, Toscano M. The molecular basis of working mechanism of natural polyphenolic antioxidants Food Chem. 2011;125:288–306
73. Eltayeb IM, Hamid AS. Phytochemical screening and antimicrobial activity of T. occidentalis seeds extracts against the isolated common skin infecting microorganisms Int J Pharm Pharm Sci. 2017;9(10):131
74. Prajapati S, Bhardwaj A, Gupta P. Antioxidant and anti-Candida activity of selected medicinal plants of Indian origin Herba Pol. 2020;66(3):1–12
75. Yong SH, Song HJ, Park DJ, Kim DH, Park KB, Choi MS. Chemical compositions and antifungal activity against Botrytis cinerea of the essential oils from the leaves of three conifer species Forest Sci Technol. 2021;17(4):169–179
76. Mohareb ASO, Badawy MEI, Abdelgaleil SAM. Antifungal activity of essential oils isolated from Egyptian plants against wood decay fungi J Wood Sd. 2013;59(6):499–505
77. Fitsev IM, Nikitin EN, Rakhmaeva AM, Terenzhev DA, Sakhno TM, Nasybullina ZR. Chemical composition of Cupressus sempervirens L. and T. occidentalis L. essential oils and their activity against phytopathogenic fungi Uchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki. 2022;164(3):392–407
78. Stan MS, Voicu SN, Caruntu S, Nica IC, Olah NK, Burtescu R, et al Antioxidant and anti-inflammatory properties of a T. occidentalis mother tincture for the treatment of ulcerative colitis Antioxidants. 2019;8(9):416
79. Gohla SH, Zeman RA, Bogel M, Jurkiewicz E, Schrum S, Haubeck HD, et al Modification of the in vitro replication of the human immunodeficiency virus HIV-1 by TPSg, a Polysaccaride fraction isolated from the Cupressaceae T. occidentalis L. (Arborvitae) Haematol Blood Transfus. 1992;35:140–149
80. Srivastava A, Jit BP, Dash R, Srivastava R, Srivastava S. T. occidentalis: An unexplored phytomedicine with
therapeutic applications CCHTS. 2023;26(1):3–13
81. Frenkel M, Mishra BM, Sen S, Yang P, Pawlus A, Vence L, et al Cytotoxic effects of ultra-diluted remedies on breast cancer cells Intern J Oncol. 2010;36(2):395–403
82. Sunila ES, Hamsa TP, Kuttan G. Effect of T. occidentalis and its polysaccharide on cell-mediated immune responses and cytokine levels of metastatic tumor-bearing animals Pharm Biol. 2011;49(10):1065–1073
83. Bagot JL. How to prescribe T. occidentalis in oncology? Analysis of the literature, study of practices and personal experience La Revue d' Homéopathie. 2020;11(3):e26–e32
84. Mukherjee A, Sikdar S, Khuda-Bukhsh AR. Evaluation of ameliorative potential of isolated flavonol fractions from T. occidentalis in lung cancer cells and in Benzo(a)pyrene induced lung toxicity in micem Int J Tradit Complement Med. 2016;1:1.
85. Loonat A, Chandran R, Pellow J, Abrahamse H. Photodynamic effects of T. occidentalis on lung cancer cells Front Pharmacol. 2022;13:928135.
86. Saha S, Bhattacharjee P, Mukherjee S, Mazumdar M, Chakraborty S, Khurana A, et al Contribution of the ROS-p53 feedback loop in Thuja induced apoptosis of mammary epithelial carcinoma cells Oncol Rep. 2014;31:1589–1598
87. Singh T, Aggarwal N, Thakur K, Chhokar A, Yadav J, Tripathi T, et al Evaluation of
therapeutic potential of selected plant-derived homeopathic medicines for their action against cervical cancer Homeopathy. 2023 doi: 10.1055/s-0042-1756436
88. Pal A, Das S, Basu S, Kundu R. Apoptotic and autophagic death union by T. occidentalis homeopathic drug in cervical cancer cells with thujone as the bioactive principle J Integ Med. 2022;20(5):463–472
89. Offergeld R, Reinecker C, Gumz E, Schrum S, Treiber R, Neth R, et al Mitogenic activity of high molecular polysaccharide fractions isolated from the cuppressaceae T. occidentalis L. enhanced cytokine-production by thyapolysaccharide, g-fraction (TPSg) Leukemia. 1992;6(3):189S–191S
90. Gohla SH, Haubeck HD, Neth RD. Mitogenic activity of high molecular polysaccharide fractions isolated from the Cupressaceae Thuja occidentale L. I. macrophage-dependent induction of CD-4-positive T-helper (Th+) lymphocytes Leukemia. 1988;2(8):528–533
91. Deb L, Dubey SK, Jain A, Jain AK, Pandian GS. Preventive effect of T. occidentalis (Linn) on gastric ulcer-a novel role of free radical scavenger J Nat Remedies. 2009;9(2):152–158
92. Das S, Rani R. Antioxidant and gastroprotective properties of the fruits of T. occidentalis Linn AJBPR. 2013;3(3):80–87
93. Sonny DR. Multiple filiform warts treated with T. occidentalis: A case report Sch Int J Tradit Complement Med. 2022;5(2):24–27
94. Dubey SK, Batra A. Hepatoprotective activity from ethanol fraction of T. occidentalis Linn Asian J Res Chem. 2008;1(1):32–35
95. Sunila ES, Kuttan G. Protective effect of T. occidentalis against radiation-induced toxicity in mice Integr Cancer Ther. 2005;4(4):322–328
96. Tyagi CK, Porwal P, Mishra N, Sharma A, Chandekar A, Punekar R, et al Antidiabetic activity of the methanolic extracts of T. occidentalis twings in alloxan-induced rats CTM. 2019;5(2):126–131
97. Gupta M, Sharma K. A review of phyto-chemical constituent and pharmacological activity of Thuja species IJPRA. 2021;6(1):85–95
98. Freeman BC, Beattie GA. An overview of plant defenses against pathogens and herbivores. The plant health instructor Photochem Photobiol. 2008;50:443–450
99. Kéïta S, Vincent C, Schmidt J, Arnason J. Insecticidal effects of T. occidentalis (Cupressaceae) essential oil on Callosobruchus maculatus [Coleoptera: Bruchidae] Can J Plant Sci. 2001;81:173–177
100. Boyko OO, Brygadyrenko VV. Nematocidial activity of aqueous solutions of plants of the families Cupressaceae, Rosaceae, Asteraceae, Fabaceae, Cannabaceae and Apiaceae Biosys Divers. 2019;27(3):227–232
101. Aziz A, Khan IA, Ahmed MB, Munawar SH, Manzoor Z, Bashir S, et al Evaluation of antipyretic activity of T. occidentalis Linn. in PGE1 and TAB-vaccine induced pyrexia models in rabbits Int J Pharm Sci. 2014;4(2):481–484
102. Rani D, Dantu PK. Screening of in vitro antileishmanial activity of extracts of selected medicinal plants Natl Acad Sci Lett. 2015;38(3):275–279
103. Gond BP. Effectiveness of T. occidentalis in the treatment of solitary nodular lesion of tongue: A case report Int J Homoeopathic Sci. 2022;6(1):35–38
104. Pal S, Dey A. Thujone in daily life-a review on natural sources of Thujone, its side effects and reduction mechanism of Thujone toxicity Biolife. 2023;11(1):21–31
105. Batiha GES, Olatunde A, El-Mleeh A, Hetta HF, Al-Rejaie S, Alghamdi S, et al Bioactive compounds, pharmacological actions, and pharmacokinetics of wormwood (Artemisia absinthium) Antibiotics (Basel). 2020;9(6):353
106. Patel R, Alavi F, Ortega S, Matela A. Herb-induced liver injury by Cimicifuga racemosa and
Thuja occidentalis herbal medications for fertility Case Rep Gastrointest Med. 2021;2021:8858310.
107. Jung J, Chun Y, Jang YP, Oh MS, Kim JH, Kim J. An alcoholic extract of Thuja orientalis L. leaves inhibits autophagy by specifically targeting pro-autophagy PIK3C3/VPS34 complex Sci Rep. 2021;11(1):17712
108. Dosoky NS, Setzer WN. Maternal reproductive toxicity of some essential oils and their constituents Int J Mol Sci. 2021;22(5):2380
109. Chahardehi AM, Arsad H, Lim V. Zebrafish as a successful animal model for screening toxicity of medicinal plants Plants (Basel). 2020;9(10):1345
Publisher’s note
The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
