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 Table of Contents  
REVIEW ARTICLES
Year : 2021  |  Volume : 12  |  Issue : 2  |  Page : 128-133

A review on ethanobotanical survey of medicinal plants available in North-East India against microbes involved in diabetic foot ulcer


1 Programme of Biotechnology, Faculty of Science, Assam Down Town University, Guwahati, Assam, India
2 Programme of Biochemistry, Faculty of Science, Assam Down Town University, Guwahati, Assam, India

Date of Submission12-Jun-2020
Date of Decision23-Jul-2020
Date of Acceptance30-Jul-2020
Date of Web Publication31-Mar-2021

Correspondence Address:
Dr. Nayan Talukdar
Programme of Biotechnology, Faculty of Science, Assam Down Town University, Guwahati, Assam.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_45_20

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  Abstract 

Diabetes mellitus is one of the most common chronic metabolic disorders, which are occurring across the globe with several complications affecting different systems of the body. One of the most devastating complications of diabetes mellitus is a diabetic foot ulcer. With the global occurrence of 6.3%, diabetic foot ulcers are commonly caused due to the severe infections caused by multidrug-resistant microorganisms such as Staphylococcus aureus, Klebsiella species, Enterococcus, Pseudomonas aeruginosa, Escherichia coli, and Proteus species and filamentous fungi such as Candida sp and Fusarium solani. Till date, medicinal plants have been traditionally used to treat several human infections. There are plants such as Santalum album, Jasminum officinale, Bergenia ciliata, and Cinnamomum tamala, which have variable antimicrobial activities. They are potentially active against microorganisms such as S. aureus, P. aeruginosa, E. coli, Klebsiella sp., and Proteus sp., which are commonly found in several human infections. Further investigations can be done to introduce the effect of various medicinal plants that can act against the microorganisms associated with diabetic foot ulcers and inhibit their growth. Northeast India being a large reservoir of diverse medicinal plants can be explored for the discovery of newer antibacterial bioactive molecules that can inhibit the growth of such microorganisms, thereby developing nature-based treatment methods which will reduce the high cost of treating diabetic foot ulcers.

Keywords: Antibacterial molecules, diabetes mellitus, diabetic foot ulcer, medicinal plants


How to cite this article:
Talukdar N, Das K, Barman I. A review on ethanobotanical survey of medicinal plants available in North-East India against microbes involved in diabetic foot ulcer. J Diabetol 2021;12:128-33

How to cite this URL:
Talukdar N, Das K, Barman I. A review on ethanobotanical survey of medicinal plants available in North-East India against microbes involved in diabetic foot ulcer. J Diabetol [serial online] 2021 [cited 2021 Apr 12];12:128-33. Available from: https://www.journalofdiabetology.org/text.asp?2021/12/2/128/312662




  Introduction Top


Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion or action.[1] There are three major types of diabetes: type 1 diabetes, type 2 diabetes, and gestational diabetes. In DM, the body is unable to regulate the amount of sugar (glucose) in the blood. Carbohydrates and sugars after ingestion are broken down into glucose (by liver) which fuels our body.[2] The glucose is then released into the blood stream. In a healthy person, the blood glucose levels are maintained primarily by insulin. People suffering from diabetes either do not produce enough insulin (type 1 diabetes) or cannot use the insulin properly (type 2 diabetes) or both. Type 1 diabetes is a condition where our immune system destroys insulin-making cells (beta cells) in our pancreas. It is also known as juvenile diabetes as it is usually diagnosed in children and young people. Type 2 diabetes is a lifelong disease that restricts our body from using insulin the way it should. Gestational diabetes is any abnormal sugar/carbohydrate intolerance that occurs during pregnancy.[3] According to WHO (World Health Organization), women with gestational diabetes are at an increased risk of complications during pregnancy and at delivery. They and their children are also at increased risk of type 2 diabetes in the future.

Consequences of diabetes include damage of heart, blood vessels, eyes, kidneys, and nerves. Healthy diet, regular physical activity, maintaining a normal body weight, medication, regular screening, and treatment for complications can help treat diabetes. Diabetic patients are well known to be at a risk of other complications such as neuropathy, macrovascular complications, retinopathy, and pedal ulcers.[4]


  Epidemiology of Diabetes Top


According to the latest 2019 data from the International Diabetes Federation, an estimated 463 million adults are living with diabetes which is likely projected to double by 2030.[5] Type 2 diabetes makes about 85%–90% of the total cases.[6] WHO estimated that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death.[7] Another 2.2 million deaths worldwide were attributed to high blood glucose levels and the increased risk of associated complications such as stroke, kidney failure, heart disease.[8] India is one of the six countries in South East Asia region that has the highest prevalence of diabetes with 8.8% of the adults being diagnosed.[9] The overall prevalence of diabetes ranges from 5% to 17% in the urban areas and 2.4%-2.7% in rural areas.[10],[11] According to National Diabetes and Diabetic Retinopathy Survey Report 2019, males within the ages 70-79 were found to be most diabetic [Figure 1]. Increase in the number of patients can be attributed to increase in urbanization, social, and cultural changes, dietary changes, reduced physical activity, and unhealthy behavior.[10]
Figure 1: Age and gender-wise prevalence of diabetes in population aged ≥ 50 years

Click here to view



  Diabetic Foot Ulcer Top


One of the most devastating complications of diabetes is diabetic foot ulcer (DFU) associated with neuropathy of the lower limb. The life-time risk of diabetic patients to develop DFU is around 25%. As studied, approximately 60%–80% of these ulcers heal, 10%–15% remain active, and 5%–24% of them finally lead to limb amputation.[12] DFUs are defined as foot lesions (ulcers) that may affect the skin, soft tissue, and bone in lower limbs, causing an aggravating infection in diabetic patients that can lead to very serious consequences such as lower-limb amputations. Diabetes is the leading cause of nontraumatic lower-extremity amputations worldwide.[13] It is estimated that 15%–25% of diabetic patients develop DFU during their life-time.[14] Treatment of infection in DFU is difficult and expensive. Moreover, the treatment is challenging and need long duration.[15]


  Microbiota in Diabetic Foot Ulcer Top


DFUs are usually polymicrobial. Commonly encountered pathogens include methicillin-resistant Staphylococcus aureus, hemolytic streptococci, Enterobacteriaceae, Pseudomonas aeruginosa, and enterococci. Anaerobes, such as bacteroides, peptococcus, and peptostreptococcus, are rarely the sole pathogens but are seen in mixed infections with aerobes. Studies conducted reveal that Staphylococcal species comprises around 24% of the isolates and out of this 55% were S. aureus. Streptococci were also cultured from around 41% of the patients with S. agalactiae comprising half of the strains. Studies show the prevalence of polymicrobial infection from the samples of diabetic patient’s foot ulcers with aerobic Gram-negative bacilli, which are the most commonly isolated microorganisms. Enterobacteriaceae, especially Proteus sp were the most frequent, whereas among the Gram-positive cocci, S. aureus were the most prevailing species. Among Gram-negative bacilli Klebsiella pneumonia was the most dominant followed by E. coli and enterobacter.[16]

Several studies have investigated the relationship between the types of infections and organisms recovered from such wound infections. Results show that most mild infections are monomicrobial and are caused by aerobic Gram-positive cocci such as S. aureus and Streptococcus spp. Further, they found that most severe infections are usually polymicrobial that are caused by aerobic Gram-positive cocci, Gram-negative bacilli such as Pseudomonas spp., E. coli, Klebsiella spp. and Proteus spp.) and anaerobes.[17] Along with the aforementioned infections, there are also studies reporting other complications such as charcot arthropathy, gangrene, cellulitis, fungal infections, callus, osteomyelitis, and necrotizing fasciitis.[18]

There are also few studies that show that filamentous fungi and yeasts are also involved in DFU. Most of the fungi involved are identified to be Candida species and Fusarium solani. It is seen that polymicrobial fungi tend to habitat in wounds as the environment there is warm and moist which favors their growth. They reside in necrotic tissues more than compared to wounds devoid of necrosis.

These microbes form biofilms, one of the major causes of most of the chronic infections which are also multidrug resistant.[19] As DFU is polymicobial, therefore the biofilm formed is multi species in nature resulting in multi-drug resistance making it challenging for treatment by conventional antibiotics.[20],[21]


  Preventive Measure for DFU Top


Some of the preventive measures as mentioned in the IWGDF (The International Working Group on the Diabetic Foot) Guidelines 2019 were as follows:

  • Identifying the at-risk foot


  • Regularly inspecting and examining the at-risk foot


  • Educating the patient, family and healthcare professionals


  • Ensuring routine wearing of appropriate footwear


  • Treating risk factors for ulceration



  •   Management of DFU and Therapeutic Approaches Top


    Foot complications are reported to be one of the most expensive complications in diabetic patients.[22] The main processes of managing these ulcers are local wound care (surgical debridement), wound dressings, wound off-loading, treatment of active infection, vascular assessment, and glycemic control.[23]Wound debridement involves removal of the necrotic tissues as well as the surrounding callus. A wide range of dressing type is available for DFUs that manage excessive wound exudates. A vital part of wound care is relieving the plantar pressure and shear stress from a DFU. It promotes healing and prevents recurrence. Off-loading can be achieved by many mechanisms, including shoe modifications, boots, and orthotic walkers.[24] The IDSA guidelines for treating an active infection mentions about biopsy of a deep tissue culture prior to antibiotic therapy. IDSA recommends 1- to 2-week antibiotic course for mild infections and 2–3 weeks for moderate to severe infections.[25] 40% of patients with DFUs are reported with the occurrence of PAD. Patients who have comorbid DFUs and PAD have slower healing, higher major amputation rates, and higher mortality rates.[26] It is widely recommended that blood glucose be optimized to improve wound healing and limit adverse effects on cellular immunity and infection.[24] There are several observational studies stating positive correlations of glycemic control with wound healing.[27]

    It has been seen that half of the DFUs can be prevented by effective education. Educating patients on self-management, maintaining self-hygiene, and health is considered to be the keystone in preventing DFUs.[28] They can be educated about the risk factors and importance of foot care that includes monitoring foot temperature, foot hygiene, proper footwear, and blood sugar control.[29]


      Topical Antiseptics and Antimicrobials Used for Treating DFUs Top


    Topical antiseptics and antimicrobials that are used for treating DFUs are targeted based on their low toxicity to the host cells.[30] Some of the topical antiseptics and antimicrobials used in treating infections of diabetic foot are as discussed below.

    Povidone iodine 10% solution

    Povidone iodine is a broad-spectrum antibacterial agent that can penetrate the bacterial biofilm and promote wound healing. It is typically used as a short-term treatment and reassessed every 2–4 weeks.[30]

    Acetic acid

    It is used as an antibacterial agent (Pseudomonas genus and other Gram-negative bacteria). It is known to inhibit fibroblastic growth and causes tissue toxicity.[31]

    Hydrogen peroxide

    It is known to be effective against Gram-positive bacteria. However, it is also linked adversely with the risk of bullae formation.[31]

    Honey

    Honey has antibiotic, antioxidant, and anti-inflammatory features that reduce wounds and burns, granting healing without any adverse outcomes. There are studies on animal model revealing that honey can stimulate wound healing. In modern years, treatment with honey produced great interest as an alternative treatment for DFUs, and different studies evaluated several properties of honey to treat DFUs at different stages.[32]

    Plant extracts

    Plants are enriched with compounds that possess anti-inflammatory and antimicrobial activity against a wide range of microorganisms. There are studies reporting the activities of plant derivatives in treating infected pedal wounds of diabetic patients. There are studies showing decrease of ulcer dimensions on application of different plant extracts combination.[33]

    Other topical antimicrobials that were studied but not found to have clear benefits include cadexomeriodine, carboxymethylcellulose hydrofiber, superoxidized solutions, tobramycin beads, and chloramine treatment.[23]


      Plant Extracts Derivatives (Herbal medicine) Against DFUs Top


    Herbal medicines are used by around 70%–80% of the population mainly in developing countries for primary healthcare as they are believed to have no side effects, cheap, and locally available.[34] Herbal medicines are traditionally used for treating skin infections including diabetic foot infections as well.[35] There are clinical studies proving their therapeutic potential against foot ulcers.[36] They can be administered either orally or topically.


      An Overview of Medicinal Plants in India Top


    Primitive records of the use of herbal medicine in India dates back to 5000 years which have been proved to be derived from the rich traditions of ancient civilizations and scientific inheritance. In India, 17,000–18,000 species of flowering plants are found of which 6000–7000 are estimated to have medicinal properties. An estimated 960 species of medicinal plants are in trade, of which 178 species have annual consumption levels more than 100 metric tons. Government of India, in November 2000 set up a board, The National Medicinal Plants Board for coordinating all matters relating to medicinal plants and support policies and programs for growth of trade, export, conservation, and cultivation of these plants.[37] As stated by the National Medicinal Plants Board, India is one of 17 mega biodiversity countries with 15 agro-climatic zones. As per data available (National Health Portal, India), around 80% of the drugs are plant based in developing countries like India. Therefore the economic importance of medicinal plants is much more in India than in other countries of the world.


      North-East India: A Reservoir of Medicinal Plants Top


    Plants are being used traditionally for thousands of years in the rural areas of the developing countries and in many parts of the world as the primary source of medicine.[38] Around the world, plants have been traditionally used for healing various ailments and compounds effective against different microbial strains have been recognized and reported.[39] North-east India, being a hub of medicinal plants, yet till date only a minimal number of species has been identified for their use as medicines in treating various diseases [Table 1]. Medicinal plants possess a wide variety of constituents for which they are considered to be a rich source of antimicrobial agents. Phytochemicals present in the plants are attributes of various bioactive compounds that are responsible for acting against different microbes. There are many plants and herbs grown in wild or some are recognized and domesticated by the natives of Assam that are known to have outstanding medicinal uses. Some are consumed in forms as spice herb and are known for their beneficial effects in maintaining good health.[40]
    Table 1: List of medicinal plants available in North-East acting against pathogens that cause DFUs

    Click here to view



      Functional Biological Molecules in Medicinal Plants as Antimicrobial Agents Top


    Since ages, researchers have been interested in plant-derived natural compounds or molecules that are capable of acting against a wide range of microbes. These compounds are known to overcome the problem of antibiotic resistance. They are a wide range of compounds that are naturally found in plants. They are known to be capable of restoring the clinical applications of older antibiotics.[49] Based on their chemical structures, they can be classified into several major groups that include alkaloids, sulfur-containing compounds, terpenoids, and polyphenols.[50] These phytochemicals have been reported to be a possible source of natural, cheap, effective, and safe antimicrobial agents.


      Conclusion Top


    DM is causing a serious threat for the human across the globe. There is also noticed that during this COVID-19 pandemic situation patients suffering from diabetes are more prone for the viral infection.[51] As 6.3% diabetic patients are suffering from DFU, early diagnosis and management of diabetes is essential. Herbal therapies are always playing a leadership role in the management of diabetes and its complications. From this article, this is noticed that microbes are predominantly available in DFU and there are several herbal formulations acting against these microbes. Hence, these herbal sources could be a potent source to control DFU with lesser side effects.

    Future scope

    This review article opens the platform for the researchers to find some herbal formulations as a product to avoid DFU.

    Financial support and sponsorship

    Nil.

    Conflicts of interest

    There are no conflicts of interest.



     
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      In this article
    Abstract
    Introduction
    Epidemiology of ...
    Diabetic Foot Ulcer
    Microbiota in Di...
    Preventive Measu...
    Management of DF...
    Topical Antisept...
    Plant Extracts D...
    An Overview of M...
    North-East India...
    Functional Biolo...
    Conclusion
    References
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