#Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases.

Artemisia is a large, diverse genus of plants with between 200 and 400 species belonging to the daisy family Asteraceae.  Common names for various species in the genus include mugwort, wormwood, and sagebrush.

Artemisia comprises hardy herbaceous plants and shrubs, which are known for the powerful chemical constituents in their essential oils.  Artemisia species grow in temperate climates of both hemispheres, usually in dry or semiarid habitats.  Notable species include A. vulgaris (common mugwort), A. tridentata (big sagebrush), A. annua (sagewort), A. absinthium (wormwood), A. dracunculus (tarragon), and A. abrotanum (southernwood).  The leaves of many species are covered with white hairs.

Artemisia annua is an herb traditionally used in Chinese medicine to treat fever, inflammation, and malaria. A compound in artemisia was shown to be effective in treating malaria in a clinical trial. Another case study showed that artemisia was effective in treating chronic bladder infrction.

Most species have strong aromas and bitter tastes from terpenoids and sesquiterpene lactones, which discourage herbivory, and may have had a selective advantage.  The small flowers are wind-pollinated.  Artemisia species are used as food plants by the larvae of a number of lepidoptera species.

Some botanists split the genus into several genera, but DNA analysis does not support the maintenance of the genera Crossostephium, Filifolium, Neopallasia, Seriphidium, and sphaeromeria; three other segregate genera– stilnolepis, Elachanthemum, and Kaschgaria– are maintained by this evidence.  Occasionally, some of the species are called sages, causing confusion with the Salvia sages in the family Lamiaceae.

Abstract

The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water , methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin E2 (PGE2) and proinflammatory cytokine (IL-1B, 1L-6, and 1L-10) production.

Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, (91.0+-3.2%), similar to a-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms. Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. Animalis, Fusobacterium nucleatum subsp. Polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases.

Keywords: Anti-inflammatory effect, Anti-microbial activity, Antioxidant activity, Artemisinin

Introduction

There has been an increase in the reevaluation of traditional medicinal plants worldwide, with extensive research on various plant species and their therapeutic properties being carried on. Traditional medicinal plant remedies have been highlighted as alternative medicines that are less likely to cause adverse side effects, unlike synthetically generated chemical substances.

Artemisia annua L. (Asteraceae) is an annual herb native to Asia, and has been used for many centruries in traditional Asian medicine for the treatment and prevention of fever and chills. A variety of compounds have been extracted from Artemisia annua L. such as sesquiterpenoids, flavonoids, coumarins, lipids, phenolics, purines, steroids, triterpenoids, aliphatics, and artemisinin.

The main component in Artemisia annua L. artemisinin, has the formula C15H22O15 and contains a peroxide bridge (C-O-O-C) (Fig.1). Artemisinin has been widely used for the treatment of malaria for the past two decades.

Additionally, artemisinin is known to have antibacterial, antifungal, antileishmanial, antioxidant, antitumor, and anti-inflammatory activity.

During inflammation macrophages are key immune cells that regulate inflammatory responses. Inflammatory responses to pathogenic microbes rely on innate and adaptive immune responses. Activated of inflammatory mediators, including interleukin (1L)-1B, 1L-6, 1L-10, prostaglandin E2 (PGE2) and nitric oxide (NO) [8,9,10]. Cytokines, such as 1L-1B, 1L-6 and 1L-10 are soluble proteins secreted by cells of the immune system. Free radicals in the form of reactive oxygen and nitrogen species are an integral part of normal physiology, and free radical reactions occur throughout the human body. Over production of these reactive stress caused by imbalances in the body’s antioxidant defense system and free radicals formation.

These reactive species can interact with biomolecules, causing cellular injury and death. Scavenging of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radicals is the basis of the widely used DPPH antioxidant assay. In the study, the in vitro antioxidant activity of Artemisia annua L extracts was evaluated using the DPPH radical scavenging assay.

Periodontal disease is a complex chronic inflammatory disorder that is one of the most prevalent microbial diseases in the world. Gram-negative anaerobic bacteria are the etiologic agents of periodontal desiase. Periodontal disease and severe periodontitis can result in periodontal destruction, pain, alveolar bone resorption, and tooth loss. Aggregatibacter actinomycetemcomitans is a gram-negative bacterium associated with a variety of infectious diseases such as nonperiodontal and urinary tract diseases, as well as general periodontal disease and localized juvenile and adult periodontitis. Members of the genus Fusobacterium are common species of human microbiota normally associated with the oral cavity, colon, genital tract, and upper respiratory tract. Fusobacterium species thrive in gingival pockets and increase in number with the progression of periodontal disease. It is one of the characteristic species frequently isolated from infected gingival pockets indicating it is a potential periodontal pathogen. Prevotella intermedia is another species that is present in generalized juvenile periodontitis and found in the gingival service of patients with periodontitis.

☆  Medicinal

Artemisinin extract from Artemisia annua L. has been used for the treatment of a variety of human illnesses as has been reported reviously. However, Artemisinin extracts generated with different solvents and their dental pharmaceutical potential have not been reported yet. In this study, artemisinin extracts from water, methanol, ethanol, and acetone were evaluated for anti-inflammatory, antioxidant, and antimicrobial effects to determine their therapeutic potential for use in dental pharmace uticals.

Preparation of Artemisinin-containing solution (ACD)

Dried Artemisia annua L. (15g) was extracted with 80% methanol, 80% ethanol, and 80% acetone under reflux for 24 hr, and the supernatants were filtered using Whatman filter paper (Macherey-Nagel, Germany). The filtered extractsmwere evaporated under reduced atmospheric pressure using a rotary evaporator (Eyela, Japan), resulting in a viscous solution. Equal volumes of Artemisia annua L. were extracted with hot water and filtered using Whatman filter paper.

The artemisinin-containing Artemisia annua L. extracts were measured by the Folin-Denis methods. Folin-Ciocalteu phenol reagent (750) was added to 150 of sample and the reaction mixture was incubated for 5 min. After incubation, 600 of 105 Na2CO3 was added and the the reaction mixture was incubated at room temperature for 1 hr. Absorbance of the reaction mixture was measured at 760nm using a microplate reader (Tecan, Mannedorf, Switzerland). Artemisinin was quantified by HPLC with a Water 1525 binary HPLC pump, Water 2707 autosampler, Waters 2489 UV/visible detector, and ODS (250×4.6mm, 5 um) Hypersil C-18 column (Thermo Fisher Scientific, Waltham, MA, USA). The mobile phase consisted of a 3:7 water:acetonitrile ratio with a flow rate of 1 ml/min. The injection volume for each sample was 10ul, and the retention time of artemisinin was approximately 15 min at 220 nm.

Artemisia annua native to China, growing in the wild, at the edges of civilization and in waste places, plant prefer full sun, requires little moisture, and tolerates a wide range of soils, growing quickly to 7 feet, flowering in dangling yellow balls.

Artemisinin (from Artemisia annua) and derivatives are a group of compounds with the most rapid action of all current agents used to treat malaria.

~  Artemisinin is a drug derived from the Asian plant Artemisia annua.  This aromatic plant has fern-like leaves and yellow flowers.

~  For more than 2,000 years, it has been used to treat fever.  It’s also an effective treatment for malaria.

~  Other potential uses include as a treatment for inflammation or bacterial infections or headaches, though there is no scientific data to support this.

Artemisia annua is known by several other names:

●  qinghaosu

●  qing hao

●  sweet wormwood

●  sweet Annie

●  sweet sagewort

●  annual wormwood

Recently, researchers have studied the effect artemisinin has on cancer cells.  However, human clinical trials and research are limited.

~  Treatment containing an artemisinin derivative (artemisinin-combination therapies) are now standard treatment worldwide for malaria caused by Plasmodium falciparum.

Artemisia cina and other Old World species are the source of the antihelminthic drug, santonin.

~  Chinese mugwort, Artemisia argyi, is used in traditional Chinese medicine.

~  In mice, artemisia capillaris Thunberg (A. capillaris) has been found to have potent sedative-hypnotic effects, which are probably mediated through potentiation of the GABA receptor CI ion channel complex.

~  In rats, artemisia austriaca has beneficial effects in reducing the withdrawal syndrome of morphine.

~  Researchers in Africa developed herbal remedies and protocols using artemisia during the Covid-19 pandemic.

Madagascar began manufacturing and distributing thr herbal drink Covid-Organics in April 2020.  In May, a team of medical researchers from the DRC, experienced with using the plant against malaria, developed medical guidelines for treating Covid-19 with artemisia.

☆  Artemisinin and Cancer

~  Researchers think artimisinin could be an alternative to more aggressive cancer therapies, with little risk of developing a drug resistance.

~  Cancer cells require iron to divide and multiply.  Iron activates artemisinin, which creates cancer-killing free radicals.

~  A 2015 study revealed artemisinin was more effective in killing cancer cells when combined with iron.

~  In addition, University of Washington researchers found artemisinin to be a thousand times more specific in killing certain cancer cells than current treatment, sparing normal cells from being destroyed while targeting cancer cells.

~  In their study, researchers bound artemisinin to cancer transferrin, a cancer-killing compound.  This combination “fools” cancer cells into treating the transferrin as a harmless protein.  Result showed that leukemia cells were destroyed and white blood cells were left unharmed.

~  Though there have been success stories with this treatment, artemisinin research is still experimental, with limited data and no large clinical trials on humans.

☆  The World Health Organization (WHO) recommend a form of Artemisinin for treating severe malaria.

●  Can Artemisinin Help Treat Cancer?

~  The Artemisia annua plant may have anticancer properties, though there is currently no strong evidence that it can help fight cancer in humans.

~  The investigations into its anticancer  properties tend to have small sample sizes or use animal models instead of humans.

~  Some researchers believe that artemisinin interacts with iron to form free radicals in the body.  Free radicals are compounds that kill cells.  Cancerous cells absorb a lot of iron, which makes them potentially much more susceptible to damage from these free radicals.

☆  A group of researchers looked at all of the research, conducted between 1983 and 2018, into the effects of artemisinin and its derivatives on cancer, and they reported the following:

●  Several studies suggest that artemisinin and its synthetic forms can target cancer cells when combined with chemotherapy.

●  Artemisinin may produce fewer side effects than traditional cancer treatments.

●  Study sizes tended to be small, which means that their results are less reliable.

●  Researchers need further studies to know how safe artemisinin is for humans and how artemisinin affects cancer cells.

●  They also need further studies to determine how artemisinin interacts with cancer drugs.

☆  Side Effects of Artemisinin

~  Artemisinin can be taken orally, injected into your muscle, or inserted into the rectum as a suppository.  This extract is associated with few side effects, but it shouldn’t be combined with other medication unless your doctor approves.

☆  Some Common Side Effects of Artemisinin are:

●  skin rash

●  nausea

●  vomiting

●  tremors

●  liver issues

~  You shouldn’t take artemisinin if you’re taking anti-seizure medications.  It can induce seizures or make the medication less effective.  People with gastrointestinal problems shouldn’t take artemisinin.

☆  Bottomline

~  Artemisinin is an effective malaria treatment and has been studied as a cancer treatment.  Early studies show promising results, but research is limited.  Also, no large clinical trials have been completed.

~  If you have cancer, you should still pursue traditional cancer treatments.  Talk with your doctor about experimental treatments, such as artemisinin, to get more information specific to your case.

References:  wikipedia / healthline.com / ncbi.nlm.gov

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