Table of Contents
Terminalia arjuna, frequently referred to as arjuna, comes from the family of Combretaceae. Its bark preparation is being utilized in the Indian subcontinent for anginal pain, hypertension, heart disease, and dyslipidemia, based on the observations of ancient physicians for centuries.It is an ayurvedic remedy that has actually been pointed out considering that vedic duration in numerous ancient Indian medicinal texts including Charaka Samhita, Sushruta Samhita, and Astang Hridayam. [1]
History
According to the Mahabharata – one of the most reputable books of Indian mythology – Arjuna was one of 5 brothers and a central character in this ancient Indian impressive. Child of the god Indra and renowned for his talent in archery, he was understood for his steadfastness and single mindedness in pursuing his objectives. His commitment to Lord Krishna earned him the divine understanding of the Bhagavad-Gita and the character of Arjuna signifies purity, stability, loyalty and valour. It is said that the hero of this epic was named after the Terminalia Arjuna tree because of its protective effects. The Arjuna herb was known for its function in protecting vitality and was nicknamed “Guardian of the Heart”, showing similar characteristics to the hero of the Indian saga. In Sanskrit the word Arjuna means “shining”, mentioning the silvery shimmering quality of the outer bark of the tree. Once a year this bark peels away to reveal the inner red recovery bark, making it available for harvest without harm to the tree. [2]
Description
Arjuna grows to about 20– 25 metres tall; usually has a buttressed trunk, and forms a large canopy at the crown, from which branches drop downwards. It has elongate, conical leaves which are green on the top and brown listed below; smooth, grey bark; it has pale yellow flowers which appear between March and June; its glabrous, 2.5 to 5 cm fibrous woody fruit, divided into five wings, appears between September and November. The tree does not struggle with any major diseases or pests, however it is prone to Phyllactinia terminale and rot due to polystictus affinis.
Circulation and environment
The arjuna is seen across the Indian Subcontinent, and typically found growing on river banks or near dry river beds in Uttar Pradesh, Bihar, Maharashtra, Madhya Pradesh, West Bengal, Odisha and south and main India, along with Sri Lanka and Bangladesh. It has likewise been planted in Malaysia, Indonesia and Kenya. [3]
Category
- Kingdom: Plantae
- Department: Magnoliophyta
- Class: Magnoliopsida
- Order: Myrtales
- Household: Combretaceae
- Genus: Terminalia
- Types: T. arjuna
- Zoological name: Terminalia arjuna
Other names: Arjuna, Koha, Kahu, Arjan, White Marudah, White Murdh, Arjuna Myrobalan, Orjun, Yerra maddi, Sadada, Sadaru and much more. [4]
Characteristics of the Arjuna Tree
Arjuna, likewise called arjun, is a marvelous, deciduous tree that can reach heights up to 100 feet and has actually been valued for its wood and therapeutic homes for generations. It grows throughout the wet, marshy, sub-Himalayan areas of India and Sri Lanka, producing clusters of small white or yellow flowers amidst its cone-shaped leaves. The most sought-after part of the tree is its red inner bark, which is respected as a tonic for the heart and is thought about comparable to hawthorn in European herbalism. The thick, white-to-pinkish-gray external bark molts naturally once a year and is collected when the trees are mature. Providing the tree time to recover and regrow its bark is an essential component to sustainable harvesting. Centuries back, the arjuna tree was offered a name befitting its conventional role of securing the heart, similar to its mythological namesake brought perseverance, strength, and security to his family in battle.The term “arjuna” means “bright,” “white,” or “shining” in Sanskrit, similar to the light-reflective bark of the arjuna tree.
Phytochemistry
The major constituents of T. arjuna in stem bark, root bark, fruits, leaves and seeds are well characterized. The initial phytochemical analysis of existing substances in T. arjuna was performed according to different standard procedures. As bark was thought about to be the most important constituent from the medical perspective, at first reported that the bark had 34% ash content consisting entirely of pure calcium carbonate. Liquid extract of T. arjuna is reported to have 23% calcium salts and 16% tannins. Organic extracts of T. arjuna bark were likewise prepared utilizing the sequential methods with a number of organic solvents such as hexane, benzene, chloroform, acetone, dichloromethane, ethyl acetate, butanol, ethanol, methanol and ether, etc, to draw out various phytochemical constituents. The chemical structures of offered compounds were verified by numerous advanced strategies like HPLC, UPLC, LC-ESI-MS/MS analysis.26, 27, 55, 56 Polyphenols, flavonoids, tannins, triterpenoids, saponins, sterols and minerals are the significant constituents of T. arjuna. Such amino acids like tryptophan, tyrosine, histidine and cysteine are likewise the main ingredients in T. arjuna. [5]
Nutrient
5 bark powder samples of Arjuna (Terminalia arjuna) having various origins including 2 industrial brand names were examined for 8 small (Al, Na, K, Mg, Ca, P, Cl, Fe) and 19 trace (As, Bachelor’s Degree, Br, Co, Cr, Cs, Cu, Eu, Hg, La, Mn, Rb, Sb, Sc, Sm, Sr, Th, V, Zn) elements by INAA. Also concentrations of Ni, Cd and Pb were figured out by AAS and of Sn by ICP-MS. Arjuna bark powder is enhanced in Ca, Mg, K Cl and Fe with considerable amounts of Mn and Numerous toxic components such as As, Hg and Pb were also spotted. [6]
Microscopy
Transverse section of fresh bark shows cork composed of evenly arranged several layers of little, tangentially lengthened cells. Listed below cork is a region of cortex, composed of thin-walled, more or less brick-shaped parenchymatous cells including cluster crystals of calcium oxalate. A few groups of sclerenchymatous pericyclic fibers are spread in the cortex. Secondary phloem consists of phloem parenchyma made up of thin-walled, polygonal cells with wavy walls including cluster crystals of calcium oxalate and pigmented cells. Phloem fibres, composed of sclerenchymatous cells, happen in groups and are scattered in the form of patches in parenchyma. Narrow and practically straight medullary rays are also present. [7]
Possible advantages
There’s minimal research study on arjunarishta, and most of it was conducted in animals. For that reason, no definitive conclusions can be made about its efficiency in human beings.
High in anti-oxidants
Antioxidants are compounds that reduce the effects of highly unstable molecules called complimentary radicals. Free extreme damage is connected to chronic conditions like heart disease, type 2 diabetes, and cancer. Numerous active ingredients in arjunarishta, such as T. arjuna, V. vinifera, and W. fruticosa, include substances that function as antioxidants, consisting of flavonoids, triterpenoids, glycosides, and phenolic acids.In test-tube and animal studies, T. arjuna, V. vinifera, and W. fruticosa anti-oxidants have actually been shown to suppress the development and spread of cancers in the stomach, liver.However, it’s uncertain whether taking arjunarishta would produce comparable results, as these studies were conducted utilizing focused extracts. It’s likewise unclear whether these advantages would apply to people.
May aid blood sugar level control
Animal research study recommends that arjunarishta and its ingredients may decrease blood glucose levels.In a mouse research study, scientists found that both arjunarishta and T. arjuna extract reduced fasting blood sugar levels substantially more than a control.Similarly, a study in rats with diabetes discovered that treatment with a T. arjuna extract for 15 days considerably minimized and stabilized fasting blood sugar level levels.Additional research studies in mice with diabetes have actually likewise found the concoction’s components to significantly reduce fasting blood sugar levels.However, arjunarishta includes jaggery– an unrefined sugar product. As such, while most of the active ingredients might assist blood glucose control in animal research studies, arjunarishta as a whole may disagree for people with diabetes.Human studies on arjunarishta’s results on blood sugar management are needed before advising it for this purpose.
Other prospective benefits
Arjunarishta and its components have actually been related to other potential advantages, consisting of:.
May minimize cancer threat. Animal and test-tube research studies suggest that particular active ingredients in arjunarishta may have anticancer residential or commercial properties. Still, human research studies are required in this area.May have anti-asthmatic homes. Animal research study recommends that some of the blend’s ingredients might have anti-asthmatic properties and help in reducing lung inflammation. Once again, human research studies are needed.May aid aerobic exercise efficiency. A research study in 30 healthy young people found that T. arjuna, an essential ingredient in arjunarishta, enhanced aerobic workout endurance. [8]
Benefits of Arjun Fruit
Gets rid of halitosis
Bad breath is one of the most common way of life problems that accompany numerous people. You would not wish to go to your work place having bad breath. Eating arjun fruit can actually improve your mouth smell and can have benefits associated with oral health. This fruit has compounds that have healing properties that can even assist your gum concerns and bleeding from the teeth. You can really have arjun fruit as soon as every morning to begin your day with a fresh mouth.
Makes Bones Stronger
If you are struggling with any type of bone problems, specifically that weakens our bones, then it can be truly efficient for you to eat arjun fruit. In the old age, people might feel this bone problems growing with time. Bones of older grownups tend to end up being weaker which is when you can actually take full advantages of arjun fruit. You can eat it raw of make a juice out of it. It might even assist you with bone conditions like osteoporosis and arthritis. It might not have the ability to treat it however can bring down its symptoms.
Lowers Teeth and Gum Problems
Oral health plays a really essential role in identifying the way of life, confidence and some other factors. Eating arjun fruit can really assist you minimize your gum issues and improve teeth health. Here are some typical oral issues that could be dealt with by eating arjun fruit in your diet plan-.
- Bleeding from the teeth
- Decreases cavities
- Tooth pain
- Pain in gums
- Bleeding gums
You can have this fruit in the form of juice, or raw. You can likewise consume arjun fruit powder and put it in the form of a paste on the area where you are facing gum or teeth problems. However, it is better to speak with a physician initially and take arjun fruit more as a treatment than a treatment.
- Enhances Heart Rate Rhythms
It has actually been observed that eating arjun fruit routinely in your diet plan can decrease the risk of heart rhythm condition. This fruit can help to preserve regular heart rate rhythm that might reduce the risk of cardiac arrest. You can also have arjun bark powder and blend it in a glass of water with some honey to purify your blood. Arjun fruit thus could be beneficial to improve heart health as well. [9]
Extract preparation
The sun dried bark of T. arjuna was brought to the lab and powdered and drawn out in water (1:8, after going through 80 mesh size) by boiling (4 h). The extracts were consequently infiltrated muslin fabric and the filtrate was spray dried. For preparation of water solution of T. arjuna extracts, dried powder (500 mg), was dissolved in pure water and then centrifuged (500g, 15 min). The supernatants were moved to micro-centrifuge tubes and stored (at − 20 ° C). The quantity of total soluble solids in supernatant was measured using gravimetric analysis which acted as the basis to formulate T. arjuna concentrations. [10]
Technique of Preparation Of Arjunarishta
The main ingredient arjuna is washed and sun-dried. It is then powdered and sieved to get rid of pollutants and solid particles.Separately, the fragrant herbs i.e. madhuka, dhataki and draksha are cleaned, dried, powdered, sieved and kept aside. The powdered arjuna bark is then immersed in a specific amount of water and allowed to soak overnight. In the early morning, the decoction is then boiled and minimized to 1/4 quantity and travelled through a muslin cloth to get rid of impurities. Add jaggery to the clear preparation, stir it appropriately and filter to get rid of solid particles. Now, put the preparation in a wide-mouthed vessel, include the powdered aromatic herbs to the filtrate and seal the opening of the container.Keep it aside in the fermentation room and allow it to ferment. Keep a check on the fermentation procedure. Once the fermentation is done, filter the fermented liquid through a muslin fabric to get rid of solid particles and impurities. The concoction is then poured in air-tight containers, kept in a cool, dry location and kept for maturation. [11]
What can I utilize it for?
Arjuna bark affects a boost in levels of superoxide dismutase, catalase and glutathione levels. This action supplies defense versus oxidative stress, with a specific affinity for heart tissue. Arjuna also displays a positive inotropic action upon heart muscle, balancing any irregular contractions and promoting a healthy blood pressure. Arjuna mediates the inhibition of cholesterol biosynthesis within the liver, enhancing cholesterol metabolism and also encouraging general hepatic cellular regeneration. Arjuna has actually shown anti-bacterial, anti-viral and anti-mutagenic activity against certain strains such as salmonella, E.coli and HIV. In addition, it has actually also shown the ability to heal harmed and wounded skin cells, and prevent the development of tumours.
Into the heart of arjuna
Arjuna is first and foremost a cardio tonic. Arjuna is specifically suggested for all heart based conditions, enhancing, nourishing and fixing heart and blood vessel tissue. It will affect a reduction in any inflammation and congestion that might be hindering heart function but also support any psychological stress and anxiety affecting the organ.The regenerative impact that this herb has on the liver, likewise makes it extremely rejuvenative to the liver as an organ, enhancing general effectiveness and metabolic process, with the included ability of improving cholesterol metabolic process. Arjuna healing procedure with a specific focus upon broken skin and bones and damage triggered by chronic viral and bacterial infection. Arjuna is specifically shown in angina, congestive heart failure, heart arrhythmia, and hypertension. All have revealed indications of enhancing in human medical trials. It has actually also been revealed to minimize human overall cholesterol and triglyceride levels. It minimizes swelling and congestion that can damage the heart. It can be utilized to deal with emotional disruption and ‘broken heart’. It enhances the muscles of the heart as well as toning the blood vessels and improving flexibility which assists to prevent hypertension. It helps to stabilize the motion of vyana vayu in the heart and control circulation. Arjuna’s affinity for the chest directs it to the lungs and to reduce efficient coughs with generous mucous in bronchitis and asthma. It can likewise deal with haemoptysis affected by increased heat and inflammation. Arjuna improves liver function and inflammation, making it highly suggested in cirrrosis. Arjuna is useful as an alterative for clearing the skin of inflammation normal in acne, acne rosacea, pruritus and urticarial.The injury healing ability of arjuna is shown in post-trauma recovery of scars, post-operative recovery and fixing fractures. It can likewise be used internally and externally for healing diabetic ulcers.The astringency of arjuna prevents early ejaculation and uterine bleeding. [12]
How to Take Arjuna
If arjuna’s heart-nourishing powers and huge selection of other advantages are calling your name, there are several methods to incorporate this herb into your routine. To determine the way that is finest method for you, just tune into any specific intentions and trust where your heart is called. And of course, if you are working with a more complicated health condition, we suggest working with an Ayurvedic practitioner for particular and customized guidance. On its own. Arjuna can be utilized on its own for those who prefer working with a single herb. The most standard technique for taking arjuna is the powder; attempt drinking it in warm water as a tea. Or attempt the liquid extract for a quick, practical option.In a supplement. Arjuna is consisted of in much of Banyan’s supplements, consisting of Heart Solution, Tension Ease, Women’s Natural Shift, Healthy Bones, and Sweet Ease. Topically. Arjuna is an ideal component for our soothing and reassuring natural oils and balms. It can be discovered in Mahanarayan Oil, Daily Massage Oil, and Breast Care Balm.
Is Arjuna Safe?
Arjuna is typically considered safe in most circumstances, making it an all set ally for lots of. That said, it’s constantly crucial to approach using herbs with care. [13]
Dose
What is the advised dosage of arjuna?
Based on clinical research done on the arjuna plant so far, the following dosages have actually been advised.
For chest pain: 500mg of the powdered bark of the arjuna plant is suggested to be taken 3 times daily, along with the conventional treatment for angina for about three months.
For cardiac arrest: 500 mg of powdered arjuna bark can be taken three times per day along with the traditional treatment for heart failure for about 2 weeks. [14]
Directions
- Arjuna bark being the main ingredient is first of all washed and left for drying in the sun.
- It is then processed to get the final product in a powdered form. Do keep in mind to sieve the powder as soon as to remove the impurities or any strong particles.
- The other herbs (madhuka, dhataki and draksha) which are utilized shall likewise be cleaned thoroughly and sun dried.
- These herbs are likewise processed to form powder. Keep all the herbs independently and sieve them when to clear the possibilities of solid impure particles.
- The powdered arjuna bark is then left in water for the soaking treatment for at least 24 hr.
- The soaked item is then boiled until the quantity is minimized to less than half. To get rid of the further possibilities of pollutants, pass it through muslin fabric.
- Now add jaggery or gud to the preparation and stir it appropriately.
- Include all the herbs and seal the container tightly.
- Allow the decoction to ferment effectively.
- As soon as the fermentation is done, filter it again utilizing muslin cloth to further purify.
- It is ready to utilize and can be kept in airtight containers. [15]
Arjuna bark for skin
The bark of Arjuna is used to cure various skin associated issues. It has antioxidant, anti-inflammatory and antimicrobial homes that assist in getting rid of skin issues.
In Ayurveda, the Arjuna tree has been referred to as a gold mine of medical residential or commercial properties. Arjuna tree, fruits, leaves and roots are utilized in Ayurveda for the treatment of lots of diseases. Let us inform you that the bark of Arjuna is utilized to remove numerous kinds of skin related problems. It has antioxidant, anti-inflammatory and antimicrobial residential or commercial properties that assist in getting rid of skin issues. In today’s article, we will inform you which skin problems are eliminated by the powder of Arjun bark–.
Dry skin
Arjun bark is an efficient medicine for those with dry skin. Its extract assists in maintaining moisture in the skin. Along with this, it increases the production of sebum in the skin. Applying a face pack made from Arjun bark on the face removes the problem of dry skin and makes the face radiance.
Great Lines and Wrinkles
Using arjuna bark on the face helps in avoiding the signs of aging. It has abundant anti-oxidant residential or commercial properties that secure the skin from damage caused by totally free radicals. Applying the bark of Arjuna on the skin tightens the skin and eliminates the issue of fine lines and wrinkles.
Itching
Arjuna bark has anti-inflammatory properties, which gets rid of the problem of swelling and inflammation on the skin. Apart from this, making use of arjuna bark is also advantageous in the problem of pimples and itching on the face. It cools the skin and eliminates the issue of itching.
Pimples
Arjun bark face pack is also an effective home remedy in the issue of acne. It has antimicrobial homes that remove the issue of acne and pimples on the skin. This.
Stains
Arjun bark face pack is really reliable for people who have the problem of blemishes on the face. Using it on the face gets rid of the problem of acne. In addition to this, the bark of Arjuna is also beneficial to get rid of the dark areas and tanning of the face.
How to make Arjuna bark face pack
- To make a face pack of Arjuna bark, take the powder of the bark of this tree.
- Now add a spoonful of raw milk or honey to it.
- Now use this paste on the affected area of your skin.
- After this wash off with clean water after 15-20 minutes [16]
Interactions with Organ Systems
Stomach
The methanolic extract of Arjuna appears to safeguard gastric tissue from lipopolysaccharide (LPS) from Heliobactor Pylori, which is known to cause ulcers. [57] This protective effect has been noted versus alcohol (7 day preload), Dexamethasone (10 day preload), and diclofenac sodium (single dose) where 100-200mg/ kg of an 80% ethanolic extract gave outright defense versus ulcer formation from Dexamethasone and alcohol, while 400mg/kg of an acute dosage conferred absolute security against Diclofenac Sodium. [58] The positive control in this research study, Rantidine (35mg/kg Diclofenac, 50mg/kg alcohol, 4mg/kg Dexamethasone) likewise gave absolute protection, [58] and these protective results versus Diclofenac have been duplicated with a methanolic extract and thought to be related to the anti-oxidative capacity.
Ears
One research study kept in mind that Arjuna extracts, particularly acetonic extraction, was able to cause death of Staphylococcus aureus germs and encompassed Escherchia Coli, Acinetobacter sp, Proteus mirabilis, and Candida albicans; [60] the authors assumed that the results suggest that Arjuna may work versus ear infections (although undoubtedly preliminary).
Liver
In separated hepatocytes (HepG2), 5-100mcg/ mL of the water extract of Arjuna has the ability to concentration dependently decrease the biomarkers of oxidation induced by TERT (pro-oxidative agent), with complimentary radicals (ROS) and lipid peroxidation (TBARS) being decreased as much as 69% and 62% respectively. [61] The decrease of antioxidant enzymes by TERT was likewise substantially attenuated approximately 60% (SOD), 82% (Catalase), and Glutathione enzymes (62-65% for peroxidase and reductase; totally preventing any decrease in Glutathione S-transferase). [61] These antioxidant results are believed to underlie outcomes attained with 50mg/kg water extract of Arjuna for 7 days prior to CCL4 caused hepatotoxicity, where Arjuna substantially prevented the increase in GPT (dosage dependent decreases approximately 50mg/kg, no added advantage at 100mg/kg), stabilized ALP, and increased hepatic levels of antioxidant levels either to manage levels (Catalase and Glutathione S-Transferase) or above control (SOD), a strength similar to Vitamin C at the very same oral doses.
Kidneys
250-500mg/ kg of a hydroalcoholic extract of Arjuna bark (not an oral research study, however the equivalent injected into perfused kidneys) appears to decrease oxidation and concomitantly increase antioxidant enzymes (Catalase and Glutathione. A conservation of anti-oxidant enzymes in reaction to CCL4 is observed to be of similar effectiveness to Vitamin C and has actually noted protective effects in the kidneys of Alloxan-induced diabetic rats at oral dosages of 250-500mg/ kg of the water extract.
Molecules that are discovered in Arjuna that have been noted to exert protective effects on kidney cells include Casuarinin, a tannin structure, with more strength than the water soluble form of Vitamin E referred to as Trolox.
Urinary Tract
In vitro, Arjuna appears to be able to lower formation rates of calcium-based kidney stones (calcium oxalate and calcium phosphate evaluated) with the butanol extract being most efficient.
Testicles
One study using arsenic-induced testicular damage in rats noted that 4 days pretreatment with isolated Arjunolic acid can avoid oxidative testicular damange and histological changes in action to arsenic. This study noted that, in vitro, the antioxidant potential of Arjunolic Acid peaked at a focused of 0.4 mg/mL and this appeared to correlated with an oral consumption of 20mg/kg (as 50mg/kg did not confer extra protective advantages) which the general protective benefit was near outright, and sligtly less reliable than 100mg/kg Vitamin C. [17]
Preventative measures:
During Pregnancy and Breastfeeding: There is no evidence that Terminalia Arjuna is potentially unsafe during pregnancy & & breastfeeding. Please stay on the safe side and avoid utilizing it during pregnancy.
Bleeding Disorders: It might slow blood clotting and threat bleeding and bruising in individuals with bleeding conditions.
Surgery: Terminalia may interfere with blood sugar level control and increase the risk of bleeding throughout surgical treatment. So stop utilizing it before 2 weeks prior to a set up surgery.
Storage:
Two years if sealed and keep away from direct sunlight. [18]
Conclusion
The eternal interest in medicinal plants has resulted in the discovery of brand-new chemical constituents and pharmacological actions of arjuna. Its efficacy as an anti-ischemic representative, a powerful antioxidant, and an antiatherogenic agent has been amply demonstrated in different speculative and clinical research studies. Nevertheless, major lacunae of these studies include the lack of phytochemical standardization of the extract, bioavailability research studies, and well-designed research studies to assess its long-term toxicity impacts. Its exact role in primary/secondary coronary avoidance needs to be investigated. In addition to this, research studies to look for the result of arjuna on CYP450 enzymes and its interactions with other drugs like statin, aspirin, angiotensin-converting enzyme (ACE) inhibitors, and β-blocker require to be designed. Increasing the awareness concerning its medicinal usage can offer a direction to the doctors to react to the difficulties in treating cardiovascular diseases. [19]
Recommendations
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220499/
- https://www.indigo-herbs.co.uk/natural-health-guide/benefits/arjuna
- https://en.wikipedia.org/wiki/Terminalia_arjuna
- http://www.ecoindia.com/flora/trees/arjun-tree.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198828/
- https://www.researchgate.net/publication/320634680_INAA_of_essential_micronutrients_in_Terminalia_arjuna_bark_powder_a_versatile_heart_tonic
- https://www.pharmacy180.com/article/arjuna-317/
- https://www.healthline.com/nutrition/arjunarishta
- https://www.sciencedirect.com/science/article/pii/S1110863013000888
- https://www.onlymyhealth.com/arjun-fruit-benefits-1652761281
- https://www.netmeds.com/health-library/post/arjunarishta-benefits-uses-ingredients-method-dosage-and-side-effects
- https://www.herbalreality.com/herb/arjuna/
- https://www.banyanbotanicals.com/info/plants/ayurvedic-herbs/arjuna-benefits/
- https://aiwo.com/blogs/blog/terminalia-arjuna-benefits-sources-and-side-effects
- https://wellversed.in/blogs/articles/what-is-arjunarishta-all-you-need-to-know
- https://hindustannewshub.com/beauty-tips/these-5-skin-problems-are-removed-by-the-bark-of-arjuna-know-how-to-make-its-face-pack/
- https://examine.com/supplements/terminalia-arjuna/research
- https://chiltanpure.com/product/arjuna-powder/
- https://www.sciencedirect.com/science/article/pii/S222541101630236X